MEG Working Memory N-Back Task Revealed Functional Deficits in Children with Mild Traumatic Brain Injury.

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive impairment in military service members and Veterans. However, the mechanism of persistent cognitive deficits including working memory (WM) dysfunction is not fully understood in mTBI. Few studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in combat-related mTBI. Study participants included 25 symptomatic active-duty service members or Veterans with combat-related mTBI and 20 healthy controls with similar combat experiences. MEG source-magnitude images were obtained for alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and low-frequency (1-7 Hz) bands. Compared with healthy combat controls, mTBI participants showed increased MEG signals across frequency bands in frontal pole (FP), ventromedial prefrontal cortex, orbitofrontal cortex (OFC), and anterior dorsolateral prefrontal cortex (dlPFC), but decreased MEG signals in anterior cingulate cortex. Hyperactivations in FP, OFC, and anterior dlPFC were associated with slower reaction times. MEG activations in lateral FP also negatively correlated with performance on tests of letter sequencing, verbal fluency, and digit symbol coding. The profound hyperactivations from FP suggest that FP is particularly vulnerable to combat-related mTBI.

Abnormal Functional Activation and Connectivity in the Working Memory Network in Early-Onset Schizophrenia

An fMRI study of cognitive activation deficits in symptom-matched first episode and chronic schizophrenia patients

Recent Neuroimaging Techniques in Mild Traumatic Brain Injury

To analyze brain activation patterns in response to tests of working memory after a mild traumatic brain injury (MTBI). Research ethics committee approval and patient written informed consent were obtained. Brain activation patterns in response to n-back working memory tasks (n = 1, 2, 3) were assessed with functional magnetic resonance (MR) imaging in 20 patients with MTBI within 1 month after their injury and in 18 healthy control subjects. In n-back working memory tasks, participants monitored a series of number stimuli and were to indicate when the presented number was the same as that presented n back previously. Nine (45%) MTBI patients underwent follow-up functional MR imaging studies 6 weeks later. Digit span, a memory test for how many numbers a person can remember in sequence, and continuous performance test (CPT), a test that measures a person's sustained and selective attention and impulsivity, were also performed before functional MR imaging studies and outside the imager for each participant. Clinical data were analyzed by using t and χ(2) tests. Within-group, between-group, and initial and follow-up differences of functional MR imaging data were analyzed by using one-sample, two-sample, and paired t tests, respectively. Groups were similar for sex (P = .75), years of education (P = .069), digit span (P = .37 for total score), CPT (P = .31, .27, and .43 for omission error, commission error, and hit reaction time, respectively), and accuracy of n-back working memory performance (P = .90, .11, and .39 for one-, two-, and three-back tasks, respectively). Brain activation patterns differed between MTBI patients and controls in response to increasing working memory loads (P < .01, uncorrected). Control subjects maintained their ability to increase activation in the working memory circuitry with each increase in working memory load. In contrast, MTBI patients were impaired in their ability to increase activation in working memory circuitry under both moderate and high working memory load conditions. However, MTBI patients did show cerebral plasticity, as evidenced by more activation in some areas outside and inside the working memory circuitry as compared with control subjects (P < .01, uncorrected). In the 6-week follow-up study, compared with baseline, MTBI patients showed an improvement of activation in response to increasing working memory loads (P < .05, uncorrected). MTBI-induced differences in working memory functional activity were observed even though differences in behavioral performance between MTBI patients and controls were absent, which suggests that this approach may increase sensitivity to MTBI compared with neuropsychological evaluation alone.

SUMMARYNeuronal oscillations are suggested to play an important role in auditory working memory (WM), but their contribution to content-specific representations has remained unclear. Here, we measure magnetoencephalography during a retro-cueing task with parametric ripple-sound stimuli, which are spectrotemporally similar to speech but resist non-auditory memory strategies. Using machine learning analyses, with rigorous between-subject cross-validation and non-parametric permutation testing, we show that memorized sound content is strongly represented in phase-synchronization patterns between subregions of auditory and frontoparietal cortices. These phase-synchronization patterns predict the memorized sound content steadily across the studied maintenance period. In addition to connectivity-based representations, there are indices of more local, “activity silent” representations in auditory cortices, where the decoding accuracy of WM content significantly increases after task-irrelevant “impulse stimuli.” Our results demonstrate that synchronization patterns across auditory sensory and association areas orchestrate neuronal coding of auditory WM content. This connectivity-based coding scheme could also extend beyond the auditory domain.

An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes

Background and objectivesMild traumatic brain injury (mTBI) frequently results in persistent cognitive deficits with limited evidence-based rehabilitation options. Visual timing deficits, potentially linked to dorsal visual pathway dysfunction, represent a promising therapeutic target. This study examined whether a novel intervention targeting dorsal visual pathways (PATH) demonstrates superior efficacy compared to conventional cognitive therapies targeting ventral pathway deficits or working memory impairments.MethodsTwenty-four participants (aged 23–62 years) with mTBI were randomized to receive one of three interventions over 12 weeks: (1) PATH training targeting dorsal visual pathway function, (2) Orientation Discrimination (OD) targeting ventral pathway pattern discrimination, both of these 20-min interventions followed by 10-min of digit memory exercises, or (3) ReCollect, working memory training. Each intervention consisted of 36 sessions (30 min each, three times weekly). Primary outcome was visual working memory (VWM) performance; secondary outcomes included processing speed, reading speed, auditory working memory, selective attention, and cognitive flexibility assessed via standardized neuropsychological measures. Magnetoencephalography (MEG) recordings during resting state and an N-Back task provided neurophysiological validation.ResultsPATH training yielded significantly greater VWM improvements (49%) compared to ReCollect (13%) and OD (8%) interventions. Repeated-measures ANOVA confirmed superior efficacy of dorsal pathway training (significant at p = 0.011). Similar gains for PATH training were also found for processing speed, reading speed, and cognitive flexibility, especially when compared to the OD group, revealing importance of strengthening the dorsal stream before digit memory exercises. MEG analysis revealed PATH-specific activation in not only bilateral dorsolateral prefrontal cortex, anterior cingulate cortex, posterior parietal cortex, superior occipital gyri, but also the left anterior temporal lobe and hippocampus, primary motor cortex, and the cerebellum, as well as lower gamma-band noise, suggesting enhanced neural timing, attention, working memory, memory consolidation and retrieval mechanisms beyond the targeted dorsal pathways.ConclusionDorsal visual pathway retraining followed by targeted working memory exercises demonstrates superior therapeutic efficacy for cognitive rehabilitation following mTBI compared to conventional approaches. The intervention promotes beneficial neuroplasticity extending to memory-related brain regions, supporting its potential as a targeted, mechanistically-informed therapy for post-concussive cognitive deficits.

Modeling neural and self-reported factors of affective distress in the relationship between pain and working memory in healthy individuals

Comparing resting-state connectivity of working memory networks in U.S. Service members with mild traumatic brain injury and posttraumatic stress disorder

Individual differences in cognitive efficiency, particularly in relation to working memory (WM), have been associated both with personality dimensions that reflect enduring regularities in brain configuration, and with short-term neural plasticity, that reflects task-related changes in brain connectivity. To elucidate the relationship of these two divergent mechanisms, we tested the hypothesis that personality dimensions, which reflect enduring aspects of brain configuration, inform about the neurobiological framework within which short-term, task-related plasticity, as measured by effective connectivity, can be facilitated or constrained. As WM consistently engages the dorsolateral prefrontal (DLPFC), parietal (PAR), and anterior cingulate cortex (ACC), we specified a WM network model with bidirectional, ipsilateral, and contralateral connections between these regions from a functional magnetic resonance imaging dataset obtained from 40 healthy adults while performing the 3-back WM task. Task-related effective connectivity changes within this network were estimated using Dynamic Causal Modelling. Personality was evaluated along the major dimensions of Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Only two dimensions were relevant to task-dependent effective connectivity. Neuroticism and Conscientiousness respectively constrained and facilitated neuroplastic responses within the WM network. These results suggest individual differences in cognitive efficiency arise from the interplay between enduring and short-term plasticity in brain configuration.

Depression is a common consequence of traumatic brain injury. Separately, spontaneous depression—arising without brain injury—has been linked to abnormal responses in motivational neural circuitry to the anticipation or receipt of rewards. It is unknown if post-injury and spontaneously occurring depression share similar phenotypic profiles. This issue is compounded by the fact that nearly all examinations of these psychiatric sequelae are post hoc: there are rarely any prospective assessments of mood and neural functioning before and after a brain injury. In this Stage 2 Registered Report, we used the Adolescent Brain Cognitive Development Consortium dataset to examine if a disruption in functional neural responses to rewards is present in patients with depression after a mild traumatic brain injury. Notably, this study provides an unparalleled opportunity to examine the trajectory of neuropsychiatric symptoms longitudinally within-subjects. This allowed us to isolate mild traumatic brain injury-specific variance independent from pre-existing functioning. Here, we focus on a case-control comparison between 43 youth who experienced a mild traumatic brain injury between MRI visits, and 43 well-matched controls. Contrary to pre-registered predictions (https://osf.io/h5uba/), there was no statistically credible increase in depression in mild traumatic brain injury cases relative to controls. Mild traumatic brain injury was associated with subtle changes in motivational neural circuit recruitment during the anticipation of incentives on the Monetary Incentive Delay paradigm. Specifically, changes in neural recruitment appeared to reflect a failure to deactivate ‘task-negative’ brain regions (ventromedial prefrontal cortex), alongside blunted recruitment of ‘task-positive’ regions (anterior cingulate, anterior insula and caudate), during the anticipation of reward and loss in adolescents following mild brain injuries. Critically, these changes in brain activity were not correlated with depressive symptoms at either visit or depression change scores before and after the brain injury. Increased time since injury was associated with a recovery of cognitive functioning—driven primarily by processing speed differences—but depression did not scale with time since injury. These cognitive changes were also uncorrelated with neural changes after mild traumatic brain injury. This report provides evidence that acquired depression may not be observed as commonly after a mild traumatic brain injury in late childhood and early adolescence, relative to findings in adult cases. Several reasons for these differing findings are considered, including sampling enrichment in retrospective cohort studies, under-reporting of depressive symptoms in parent-report data, and neuroprotective factors in childhood and adolescence.

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

PTSD and Combat-Related Injuries: Functional Neuroanatomy

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose due to lack of obvious external injuries and because the injuries are often not visible on conventional acute MRI or CT. Injured brain tissues in TBI patients generate pathological low-frequency neuronal magnetic signal (delta waves 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We hypothesize that abnormal MEG delta waves originate from gray matter neurons that experience de-afferentation due to axonal injury to the underlying white matter fiber tracts, which is manifested on diffusion tensor imaging (DTI) as reduced fractional anisotropy. The present study used a neuroimaging approach integrating findings of magnetoencephalography (MEG) and diffusion tensor imaging (DTI), evaluating their utility in diagnosing mild TBI in 10 subjects in whom conventional CT and MRI showed no visible lesions in 9. The results show: (1) the integrated approach with MEG and DTI is more sensitive than conventional CT and MRI in detecting subtle neuronal injury in mild TBI; (2) MEG slow waves in mild TBI patients originate from cortical gray matter areas that experience de-afferentation due to axonal injuries in the white matter fibers with reduced fractional anisotropy; (3) findings from the integrated imaging approach are consistent with post-concussive symptoms; (4) in some cases, abnormal MEG delta waves were observed in subjects without obvious DTI abnormality, indicating that MEG may be more sensitive than DTI in diagnosing mild TBI.