Cognitive components of aging-related increase in word-finding difficulty.

Word-finding difficulty (WFD) is a common cognitive complaint in aging, manifesting both in natural speech and in controlled laboratory tests. Various theories of cognitive aging have addressed WFD, and understanding its underlying mechanisms can help to clarify whether it has diagnostic value for neurodegenerative disease. Two influential "information-universal" theories attribute it to rather broad changes in cognition. The processing speed theory posits a general slowdown of all cognitive processes, while the inhibitory deficit hypothesis (IDH) predicts a specific problem in suppressing irrelevant information. One "information specific" theory of language production, the transmission deficit hypothesis (TDH), posits a breakdown in retrieval of phonological word forms from a corresponding lemma. To adjudicate between these accounts, we administered an online gamified covert naming task featuring picture-word interference (PWI), previously validated to elicit similar semantic interference and phonological facilitation effects as overt naming tasks. 125 healthy adults aged 18 to 85 completed the task, along with a battery of executive function tasks and a naturalistic speech sample to quantify WFD in connected speech. PWI effects provided strong support for the TDH but limited support for IDH, in that semantic interference increased and phonological facilitation decreased across the lifespan. However, neither of these effects on single-word retrieval associated with WFD measured in connected speech. Rather, overall reaction time for word retrieval (controlling for psychomotor slowing) was the best predictor of spontaneous WFD and executive function decline, suggesting processing speed as the key factor, and that verbal reaction time may be an important clinical measure.

Blink-Related Oscillations Provide Naturalistic Assessments of Brain Function and Cognitive Workload within Complex Real-World Multitasking Environments.

BACKGROUND: There is a significant need to monitor human cognitive performance in complex environments, with one example being pilot performance. However, existing assessments largely focus on subjective experiences (e.g., questionnaires) and the evaluation of behavior (e.g., aircraft handling) as surrogates for cognition or utilize brainwave measures which require artificial setups (e.g., simultaneous auditory stimuli) that intrude on the primary tasks. Blink-related oscillations (BROs) are a recently discovered neural phenomenon associated with spontaneous blinking that can be captured without artificial setups and are also modulated by cognitive loading and the external sensory environment-making them ideal for brain function assessment within complex operational settings. METHODS: Electroencephalography (EEG) data were recorded from eight adult participants (five F, M = 21.1 years) while they completed the Multi-Attribute Task Battery under three different cognitive loading conditions. BRO responses in time and frequency domains were derived from the EEG data, and comparisons of BRO responses across cognitive loading conditions were undertaken. Simultaneously, assessments of blink behavior were also undertaken. RESULTS: Blink behavior assessments revealed decreasing blink rate with increasing cognitive load (p < 0.001). Prototypical BRO responses were successfully captured in all participants (p < 0.001). BRO responses reflected differences in task-induced cognitive loading in both time and frequency domains (p < 0.05). Additionally, reduced pre-blink theta band desynchronization with increasing cognitive load was also observed (p < 0.05). CONCLUSION: This study confirms the ability of BRO responses to capture cognitive loading effects as well as preparatory pre-blink cognitive processes in anticipation of the upcoming blink during a complex multitasking situation. These successful results suggest that blink-related neural processing could be a potential avenue for cognitive state evaluation in operational settings-both specialized environments such as cockpits, space exploration, military units, etc. and everyday situations such as driving, athletics, human-machine interactions, etc.-where human cognition needs to be seamlessly monitored and optimized.

Contrasting MEG effects of anodal and cathodal high-definition TDCS on sensorimotor activity during voluntary finger movements.

Introduction: Protocols for noninvasive brain stimulation (NIBS) are generally categorized as "excitatory" or "inhibitory" based on their ability to produce short-term modulation of motor-evoked potentials (MEPs) in peripheral muscles, when applied to motor cortex. Anodal and cathodal stimulation are widely considered excitatory and inhibitory, respectively, on this basis. However, it is poorly understood whether such polarity-dependent changes apply for neural signals generated during task performance, at rest, or in response to sensory stimulation. Methods: To characterize such changes, we measured spontaneous and movement-related neural activity with magnetoencephalography (MEG) before and after high-definition transcranial direct-current stimulation (HD-TDCS) of the left motor cortex (M1), while participants performed simple finger movements with the left and right hands. Results: Anodal HD-TDCS (excitatory) decreased the movement-related cortical fields (MRCF) localized to left M1 during contralateral right finger movements while cathodal HD-TDCS (inhibitory), increased them. In contrast, oscillatory signatures of voluntary motor output were not differentially affected by the two stimulation protocols, and tended to decrease in magnitude over the course of the experiment regardless. Spontaneous resting state oscillations were not affected either. Discussion: MRCFs are thought to reflect reafferent proprioceptive input to motor cortex following movements. Thus, these results suggest that processing of incoming sensory information may be affected by TDCS in a polarity-dependent manner that is opposite that seen for MEPs-increases in cortical excitability as defined by MEPs may correspond to reduced responses to afferent input, and vice-versa.

Enhanced mind-matter interactions following rTMS induced frontal lobe inhibition.

A major barrier to acceptance of psi is that effects are small and hard to replicate. To address this issue, we developed a novel neurobiological model to study this controversial phenomenon based upon the concept that the brain may act as a psi-inhibitory filter. Our previous research in individuals with frontal lobe damage suggests that this filter includes the left medial middle frontal region. We report our findings in healthy participants with rTMS induced reversible brain lesions. In support of our a priori hypothesis, we found a significant psi effect following rTMS inhibition of the left medial middle frontal lobe. This significant effect was found using a post hoc weighting procedure aligned with our overarching hypothesis. This suggests that the brain may inhibit psi and that individuals with neurological or reversible rTMS induced frontal lesions may comprise an enriched sample for detection and replication of this controversial phenomenon. Our findings are potentially transformative for the way we view interactions between the brain and seemingly random events.

Improvement in executive function for older adults through smartphone apps: a randomized clinical trial comparing language learning and brain training.

Bilingualism has been linked to improved executive function and delayed onset of dementia, but it is unknown whether similar benefits can be obtained later in life through deliberate intervention. Given the logistical hurdles of second language acquisition in a randomized trial for older adults, few interventional studies have been done thus far. However, recently developed smartphone apps offer a convenient means to acquire skills in a second language and can be compared with brain training apps specifically designed to improve executive function. In a randomized clinical trial, 76 adults aged 65-75 were assigned to either 16 weeks of Spanish learning using the app Duolingo 30 minutes a day, an equivalent amount of brain training using the app BrainHQ, or a waitlist control condition. Executive function was assessed before and after the intervention with preregistered (NCT03638882) tests previously linked to better performance in bilinguals. For two of the primary measures: incongruent Stroop color naming and 2-back accuracy, Duolingo provided equivalent benefits as BrainHQ compared to a control group. On reaction time for N-back and Simon tests, the BrainHQ group alone experienced strong gains over the other two groups. Duolingo was rated as more enjoyable. These results suggest that app-based language learning may provide some similar benefits as brain training in improving executive function in seniors but has less impact on processing speed. However, future advancements in app design may optimize not only the acquisition of the target language but also the side benefits of the language learning experience.

Asynchronous, online spaced-repetition training alleviates word-finding difficulties in aphasia.

Word-finding difficulties for naming everyday objects are often prevalent in aphasia. Traditionally, treating these difficulties has involved repeated drilling of troublesome items with a therapist. Spaced repetition schedules can improve the efficiency of such training. However, spaced repetition in a therapy environment can be both difficult to implement and time-consuming. The current study evaluated the potential utility of automated, asynchronous, online spaced repetition training for the treatment of word-finding difficulties in individuals with aphasia. Twenty-one participants completed a two-week training study, completing approximately 60 minutes per day of asynchronous online drilling. The training items were identified using a pretest, and word-finding difficulties were evaluated both at the end of training (i.e., a post-test) and four weeks later (i.e., a retention test). The trained items were separated into three different spaced-repetition schedules: (1) Short-spacing; (2) Long-spacing; and (3) Adaptive-spacing. At the retention-test, all trained items outperformed non-trained items in terms of accuracy and reaction time. Further, preliminary evidence suggested a potential reaction time advantage for the adaptive-spacing condition. Overall, online, asynchronous spaced repetition training appears to be effective in treating word-finding difficulties in aphasia. Further research will be required to determine if different spaced repetition schedules can be leveraged to enhance this effect.

Spectral slowing in chronic stroke reflects abnormalities in both periodic and aperiodic neural dynamics.

Decades of electrophysiological work have demonstrated the presence of "spectral slowing" in stroke patients - a prominent shift in the power spectrum towards lower frequencies, most evident in the vicinity of the lesion itself. Despite the reliability of this slowing as a marker of dysfunctional tissue across patient groups as well as animal models, it has yet to be explained in terms of the pathophysiological processes of stroke. To do so requires clear understanding of the neural dynamics that these differences represent, acknowledging the often overlooked fact that spectral power reflects more than just the amplitude of neural oscillations. To accomplish this, we used a combination of frequency domain and time domain measures to disambiguate and quantify periodic (oscillatory) and aperiodic (non-oscillatory) neural dynamics in resting state magnetoencephalography (MEG) recordings from chronic stroke patients. We found that abnormally elevated low frequency power in these patients was best explained by a steepening of the aperiodic component of the power spectrum, rather than an enhancement of low frequency oscillations, as is often assumed. However, genuine oscillatory activity at higher frequencies was also found to be abnormal, with patients showing alpha slowing and diminished oscillatory activity in the beta band. These aperiodic and periodic abnormalities were found to covary, and could be detected even in the un-lesioned hemisphere, however they were most prominent in perilesional tissue, where their magnitude was predictive of cognitive impairment. This work redefines spectral slowing as a pattern of changes involving both aperiodic and periodic neural dynamics and narrows the gap in understanding between non-invasive markers of dysfunctional tissue and disease processes responsible for altered neural dynamics.

Electrophysiological connectivity markers of preserved language functions in post-stroke aphasia.

Post-stroke aphasia is a consequence of localized stroke-related damage as well as global disturbances in a highly interactive and bilaterally-distributed language network. Aphasia is increasingly accepted as a network disorder and it should be treated as such when examining the reorganization and recovery mechanisms after stroke. In the current study, we sought to investigate reorganized patterns of electrophysiological connectivity, derived from resting-state magnetoencephalography (rsMEG), in post-stroke chronic (>6 months after onset) aphasia. We implemented amplitude envelope correlations (AEC), a metric of connectivity commonly used to describe slower aspects of interregional communication in resting-state electrophysiological data. The main focus was on identifying the oscillatory frequency bands and frequency-specific spatial topology of connections associated with preserved language abilities after stroke. RsMEG was recorded for 5 min in 21 chronic stroke survivors with aphasia and in 20 matched healthy controls. Source-level MEG activity was reconstructed and summarized within 72 atlas-defined brain regions (or nodes). A 72 × 72 leakage-corrected connectivity (of AEC) matrix was obtained for frequencies from theta to low-gamma (4-50 Hz). Connectivity was compared between groups, and, the correlations between connectivity and subscale scores from the Western Aphasia Battery (WAB) were evaluated in the stroke group, using partial least squares analyses. Posthoc multiple regression analyses were also conducted on a graph theory measure of node strengths, derived from significant connectivity results, to control for node-wise properties (local spectral power and lesion sizes) and demographic and stroke-related variables. Connectivity among the left hemisphere regions, i.e. those ipsilateral to the stroke lesion, was greatly reduced in stroke survivors with aphasia compared to matched healthy controls in the alpha (8-13 Hz; p = 0.011) and beta (15-30 Hz; p = 0.001) bands. The spatial topology of hypoconnectivity in the alpha vs. beta bands was distinct, revealing a greater involvement of ventral frontal, temporal and parietal areas in alpha, and dorsal frontal and parietal areas in beta. The node strengths from alpha and beta group differences remained significant after controlling for nodal spectral power. AEC correlations with WAB subscales of object naming and fluency were significant. Greater alpha connectivity was associated with better naming performance (p = 0.045), and greater connectivity in both the alpha (p = 0.033) and beta (p = 0.007) bands was associated with better speech fluency performance. The spatial topology was distinct between these frequency bands. The node strengths remained significant after controlling for age, time post stroke onset, nodal spectral power and nodal lesion sizes. Our findings provide important insights into the electrophysiological connectivity profiles (frequency and spatial topology) potentially underpinning preserved language abilities in stroke survivors with aphasia.

Investigating the Effects of Auditory and Vibrotactile Rhythmic Sensory Stimulation on Depression: An EEG Pilot Study.

Background Major depressive disorder (MDD) is a persistent psychiatric condition and one of the leading causes of global disease burden. In a previous study, we investigated the effects of a five-week intervention consisting of rhythmic gamma frequency (30-70 Hz) vibroacoustic stimulation in 20 patients formally diagnosed with MDD. In that study, the findings suggested a significant clinical improvement in depression symptoms as measured using the Montgomery-Asberg Depression Rating Scale (MADRS), with 37% of participants meeting the criteria for clinical response. The goal of the present research was to examine possible changes from baseline to posttreatment in resting-state electroencephalography (EEG) recordings using the same treatment protocol and to characterize basic changes in EEG related to treatment response. Materials and methods The study sample consisted of 19 individuals aged 18-70 years with a clinical diagnosis of MDD. The participants were assessed before and after a five-week treatment period, which consisted of listening to an instrumental musical track on a vibroacoustic device, delivering auditory and vibrotactile stimulus in the gamma-band range (30-70 Hz, with particular emphasis on 40 Hz). The primary outcome measure was the change in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to posttreatment and resting-state EEG. Results Analysis comparing MADRS score at baseline and post-intervention indicated a significant change in the severity of depression symptoms after five weeks (t = 3.9923, df = 18, p = 0.0009). The clinical response rate was 36.85%. Resting-state EEG power analysis revealed a significant increase in occipital alpha power (t = -2.149, df = 18, p = 0.04548), as well as an increase in the prefrontal gamma power of the responders (t = 2.8079, df = 13.431, p = 0.01442). Conclusions The results indicate that improvements in MADRS scores after rhythmic sensory stimulation (RSS) were accompanied by an increase in alpha power in the occipital region and an increase in gamma in the prefrontal region, thus suggesting treatment effects on cortical activity in depression. The results of this pilot study will help inform subsequent controlled studies evaluating whether treatment response to vibroacoustic stimulation constitutes a real and replicable reduction of depressive symptoms and to characterize the underlying mechanisms.

Electrophysiological abnormalities as indicators of early-stage pathology in Primary Progressive Aphasia (PPA): A case study in semantic variant PPA.

Language induced and spontaneous oscillatory activity was measured using MEG in a patient with the semantic variant of Primary Progressive Aphasia (svPPA) and 15 healthy controls.The patient showed oscillatory slowing in the left anterior temporal lobe (ATL) that extended into non-atrophied brain tissue in left and right frontal areas. The white matter connections were reduced to the left and right ATL and left frontal regions, exhibiting electrophysiological abnormalities. Altered diffusion metrics in all four language tracts, indicted compromised white matter integrity. Task-related and spontaneous oscillatory abnormalities can indicate early neurodegeneration in svPPA, providing promising targets for intervention.

Simultaneous Normalization and Compensatory Changes in Right Hemisphere Connectivity during Aphasia Therapy.

Changes in brain connectivity during language therapy were examined among participants with aphasia (PWA), aiming to shed light on neural reorganization in the language network. Four PWA with anomia following left hemisphere stroke and eight healthy controls (HC) participated in the study. Two fMRI scans were administered to all participants with a 3.5-month interval. The fMRI scans included phonological and semantic tasks, each consisting of linguistic and perceptual matching conditions. Between the two fMRI scans, PWA underwent Phonological Components Analysis treatment. Changes in effective connectivity during the treatment were examined within right hemisphere (RH) architecture. The results illustrate that following the treatment, the averaged connectivity of PWA across all perceptual and linguistic conditions in both tasks increased resemblance to HC, reflecting the normalization of neural processes associated with silent object name retrieval. In contrast, connections that were specifically enhanced by the phonological condition in PWA decreased in their resemblance to HC, reflecting emerging compensatory reorganization in RH connectivity to support phonological processing. These findings suggest that both normalization and compensation play a role in neural language reorganization at the chronic stage, occurring simultaneously in the same brain.

Engagement of Language and Domain General Networks during Word Monitoring in a Native and Unknown Language.

Functional neuroimaging studies have highlighted the roles of three networks in processing language, all of which are typically left-lateralized: a ventral stream involved in semantics, a dorsal stream involved in phonology and speech production, and a more dorsal "multiple demand" network involved in many effortful tasks. As lateralization in all networks may be affected by life factors such as age, literacy, education, and brain pathology, we sought to develop a task paradigm with which to investigate the engagement of these networks, including manipulations to selectively emphasize semantic and phonological processing within a single task performable by almost anyone regardless of literacy status. In young healthy participants, we administered an auditory word monitoring task, in which participants had to note the occurrence of a target word within a continuous story presented in either their native language, Portuguese, or the unknown language, Japanese. Native language task performance activated ventral stream language networks, left lateralized but bilateral in the anterior temporal lobe. Unfamiliar language performance, being more difficult, activated left hemisphere dorsal stream structures and the multiple demand network bilaterally, but predominantly in the right hemisphere. These findings suggest that increased demands on phonological processing to accomplish word monitoring in the absence of semantic support may result in the bilateral recruitment of networks involved in speech perception under more challenging conditions.

Contralesional Cathodal Transcranial Direct Current Stimulation Does Not Enhance Upper Limb Function in Subacute Stroke: A Pilot Randomized Clinical Trial.

Transcranial direct current stimulation (tDCS) has the potential to improve upper limb motor outcomes after stroke. According to the assumption of interhemispheric inhibition, excessive inhibition from the motor cortex of the unaffected hemisphere to the motor cortex of the affected hemisphere may worsen upper limb motor recovery after stroke. We evaluated the effects of active cathodal tDCS of the primary motor cortex of the unaffected hemisphere (ctDCSM1UH) compared to sham, in subjects within 72 hours to 6 weeks post ischemic stroke. Cathodal tDCS was intended to inhibit the motor cortex of the unaffected hemisphere and hence decrease the inhibition from the unaffected to the affected hemisphere and enhance motor recovery. We hypothesized that motor recovery would be greater in the active than in the sham group. In addition, greater motor recovery in the active group might be associated with bigger improvements in measures in activity and participation in the active than in the sham group. We also explored, for the first time, changes in cognition and sleep after ctDCSM1UH. Thirty subjects were randomized to six sessions of either active or sham ctDCSM1UH as add-on interventions to rehabilitation. The NIH Stroke Scale (NIHSS), Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA), Barthel Index (BI), Stroke Impact Scale (SIS), and Montreal Cognitive Assessment (MoCA) were assessed before, after treatment, and three months later. In the intent-to-treat (ITT) analysis, there were significant GROUP∗TIME interactions reflecting stronger gains in the sham group for scores in NIHSS, FMA, BI, MoCA, and four SIS domains. At three months post intervention, the sham group improved significantly compared to posttreatment in FMA, NIHSS, BI, and three SIS domains while no significant changes occurred in the active group. Also at three months, NIHSS improved significantly in the sham group and worsened significantly in the active group. FMA scores at baseline were higher in the active than in the sham group. After adjustment of analysis according to baseline scores, the between-group differences in FMA changes were no longer statistically significant. Finally, none of the between-group differences in changes in outcomes after treatment were considered clinically relevant. In conclusion, active CtDCSM1UH did not have beneficial effects, compared to sham. These results were consistent with other studies that applied comparable tDCS intensities/current densities or treated subjects with severe upper limb motor impairments during the first weeks post stroke. Dose-finding studies early after stroke are necessary before planning larger clinical trials.

Sensitivity of amplitude and phase based MEG measures of interhemispheric connectivity during unilateral finger movements.

Interactions between different brain regions can be revealed by dependencies between their neuronal oscillations. We examined the sensitivity of different oscillatory connectivity measures in revealing interhemispheric interactions between primary motor cortices (M1s) during unilateral finger movements. Based on frequency, amplitude, and phase of the oscillations, a number of metrics have been developed to measure connectivity between brain regions, and each metric has its own strengths, weaknesses, and pitfalls. Taking advantage of the well-known movement-related modulations of oscillatory amplitude in M1s, this study compared and contrasted a number of leading connectivity metrics during distinct phases of oscillatory power changes. Between M1s during unilateral movements, we found that phase-based metrics were effective at revealing connectivity during the beta (15-35 Hz) rebound period linked to movement termination, but not during the early period of beta desynchronization occurring during the movement itself. Amplitude correlation metrics revealed robust connectivity during both periods. Techniques for estimating the direction of connectivity had limited success. Granger Causality was not well suited to studying these connections because it was strongly confounded by differences in signal-to-noise ratio linked to modulation of beta amplitude occurring during the task. Phase slope index was suggestive but not conclusive of a unidirectional influence between motor cortices during the beta rebound. Our findings suggest that a combination of amplitude and phase-based metrics is likely required to fully characterize connectivity during task protocols that involve modulation of oscillatory power, and that amplitude-based metrics appear to be more sensitive despite the lack of directional information.

Canadian Platform for Trials in Noninvasive Brain Stimulation (CanStim) Consensus Recommendations for Repetitive Transcranial Magnetic Stimulation in Upper Extremity Motor Stroke Rehabilitation Trials.

Objective. To develop consensus recommendations for the use of repetitive transcranial magnetic stimulation (rTMS) as an adjunct intervention for upper extremity motor recovery in stroke rehabilitation clinical trials. Participants. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) convened a multidisciplinary team of clinicians and researchers from institutions across Canada to form the CanStim Consensus Expert Working Group. Consensus Process. Four consensus themes were identified: (1) patient population, (2) rehabilitation interventions, (3) outcome measures, and (4) stimulation parameters. Theme leaders conducted comprehensive evidence reviews for each theme, and during a 2-day Consensus Meeting, the Expert Working Group used a weighted dot-voting consensus procedure to achieve consensus on recommendations for the use of rTMS as an adjunct intervention in motor stroke recovery rehabilitation clinical trials. Results. Based on best available evidence, consensus was achieved for recommendations identifying the target poststroke population, rehabilitation intervention, objective and subjective outcomes, and specific rTMS parameters for rehabilitation trials evaluating the efficacy of rTMS as an adjunct therapy for upper extremity motor stroke recovery. Conclusions. The establishment of the CanStim platform and development of these consensus recommendations is a first step toward the translation of noninvasive brain stimulation technologies from the laboratory to clinic to enhance stroke recovery.

Picture-Word Interference Effects Are Robust With Covert Retrieval, With and Without Gamification.

The picture-word interference (PWI) paradigm has been used to investigate the time course of processes involved in word retrieval, but is challenging to implement online due to dependence on measurements of vocal reaction time. We performed a series of four experiments to examine picture-word interference and facilitation effects in a form of covert picture naming, with and without gamification. A target picture was accompanied by an audio word distractor that was either unrelated, phonologically-related, associatively-related, or categorically-related to the picture. Participants were instructed to judge whether the name of the target picture ended in the phoneme assigned to the block by pressing corresponding keys as quickly and accurately as possible. Experiments 1 and 2 successfully replicated categorical interference and phonological facilitation effects at different optimal stimulus-onset-asynchronies (SOAs) between words and pictures. Experiment 3 demonstrated that a key gamification feature (collecting coins) motivated faster speed at the expense of accuracy in the gamified vs. experimental format of the task. Experiment 4 adopted the optimal SOAs and verified that the gamification reveals expected interference and facilitation effects despite the speed-accuracy tradeoff. These studies confirmed that categorical interference occurs earlier than phonological facilitation, while both processes are independent from articulation and inherent to word retrieval itself. The covert PWI paradigm and its gamification have methodological value for neuroimaging studies in which articulatory artifacts obscure word retrieval processes, and may be developed into potential online word-finding assessments that can reveal word retrieval difficulties with greater sensitivity.