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OBJECTIVE: The authors sought to identify predictive factors of new-onset or novel oppositional defiant disorder or conduct disorder assessed 24 months after traumatic brain injury (TBI). METHODS: Children ages 5 to 14 years who had experienced TBI were recruited from consecutive hospital admissions. Soon after injury, participants were assessed for preinjury characteristics, including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, and family function, and the presence and location of lesions were documented by MRI. Psychiatric outcomes, including novel oppositional defiant disorder or conduct disorder, were assessed 24 months after injury. RESULTS: Of the children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified who were recruited in this study, 165 were included in this sample; 95 of these children returned for the 24-month assessment. Multiple imputation was used to address attrition. The prevalence of novel oppositional defiant disorder or conduct disorder was 23.7 out of 165 (14%). In univariable analyses, novel oppositional defiant disorder or conduct disorder was significantly associated with psychosocial adversity (p=0.049) and frontal white matter lesions (p=0.016) and was marginally but not significantly associated with SES. In the final multipredictor model, frontal white matter lesions were significantly associated with novel oppositional defiant disorder or conduct disorder (p=0.021), and psychosocial adversity score was marginally but not significantly associated with the outcome. The odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel depressive disorder was significantly higher for girls than boys (p=0.025), and the odds ratio of novel oppositional defiant disorder or conduct disorder among the children with versus those without novel attention-deficit hyperactivity disorder (ADHD) was significantly higher for boys than girls (p=0.006). CONCLUSION: Approximately 14% of children with TBI developed oppositional defiant disorder or conduct disorder. The risk for novel oppositional defiant disorder or conduct disorder can be understood from a biopsychosocial perspective. Sex differences were evident for comorbid novel depressive disorder and comorbid novel ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Lesões Encefálicas Traumáticas , Transtorno da Conduta , Criança , Humanos , Adolescente , Feminino , Masculino , Transtorno da Conduta/complicações , Transtorno da Conduta/epidemiologia , Transtorno da Conduta/psicologia , Transtorno Desafiador Opositor , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Comorbidade , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/epidemiologiaRESUMO
Advancements in deep learning algorithms over the past decade have led to extensive developments in brain-computer interfaces (BCI). A promising imaging modality for BCI is magnetoencephalography (MEG), which is a non-invasive functional imaging technique. The present study developed a MEG sensor-based BCI neural network to decode Rock-Paper-scissors gestures (MEG-RPSnet). Unique preprocessing pipelines in tandem with convolutional neural network deep-learning models accurately classified gestures. On a single-trial basis, we found an average of 85.56% classification accuracy in 12 subjects. Our MEG-RPSnet model outperformed two state-of-the-art neural network architectures for electroencephalogram-based BCI as well as a traditional machine learning method, and demonstrated equivalent and/or better performance than machine learning methods that have employed invasive, electrocorticography-based BCI using the same task. In addition, MEG-RPSnet classification performance using an intra-subject approach outperformed a model that used a cross-subject approach. Remarkably, we also found that when using only central-parietal-occipital regional sensors or occipitotemporal regional sensors, the deep learning model achieved classification performances that were similar to the whole-brain sensor model. The MEG-RSPnet model also distinguished neuronal features of individual hand gestures with very good accuracy. Altogether, these results show that noninvasive MEG-based BCI applications hold promise for future BCI developments in hand-gesture decoding.
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Interfaces Cérebro-Computador , Aprendizado Profundo , Humanos , Magnetoencefalografia , Gestos , Eletroencefalografia/métodos , AlgoritmosRESUMO
Combat-related mild traumatic brain injury (cmTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral disabilities in Veterans and active-duty military personnel. Accurate diagnosis of cmTBI is challenging since the symptom spectrum is broad and conventional neuroimaging techniques are insensitive to the underlying neuropathology. The present study developed a novel deep-learning neural network method, 3D-MEGNET, and applied it to resting-state magnetoencephalography (rs-MEG) source-magnitude imaging data from 59 symptomatic cmTBI individuals and 42 combat-deployed healthy controls (HCs). Analytic models of individual frequency bands and all bands together were tested. The All-frequency model, which combined delta-theta (1-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-80 Hz) frequency bands, outperformed models based on individual bands. The optimized 3D-MEGNET method distinguished cmTBI individuals from HCs with excellent sensitivity (99.9 ± 0.38%) and specificity (98.9 ± 1.54%). Receiver-operator-characteristic curve analysis showed that diagnostic accuracy was 0.99. The gamma and delta-theta band models outperformed alpha and beta band models. Among cmTBI individuals, but not controls, hyper delta-theta and gamma-band activity correlated with lower performance on neuropsychological tests, whereas hypo alpha and beta-band activity also correlated with lower neuropsychological test performance. This study provides an integrated framework for condensing large source-imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI. The all-frequency model offered more discriminative power than each frequency-band model alone. This approach offers an effective path for optimal characterization of behaviorally relevant neuroimaging features in neurological and psychiatric disorders.
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Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/fisiopatologia , Distúrbios de Guerra/diagnóstico por imagem , Distúrbios de Guerra/fisiopatologia , Conectoma/normas , Aprendizado Profundo , Magnetoencefalografia/normas , Adulto , Conectoma/métodos , Humanos , Magnetoencefalografia/métodos , Masculino , Sensibilidade e Especificidade , Adulto JovemRESUMO
Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members and veterans. Recent animal studies show that GABA-ergic parvalbumin-positive interneurons are susceptible to brain injury, with damage causing abnormal increases in spontaneous gamma-band (30-80 Hz) activity. We investigated spontaneous gamma activity in individuals with mTBI using high-resolution resting-state magnetoencephalography source imaging. Participants included 25 symptomatic individuals with chronic combat-related blast mTBI and 35 healthy controls with similar combat experiences. Compared with controls, gamma activity was markedly elevated in mTBI participants throughout frontal, parietal, temporal, and occipital cortices, whereas gamma activity was reduced in ventromedial prefrontal cortex. Across groups, greater gamma activity correlated with poorer performances on tests of executive functioning and visuospatial processing. Many neurocognitive associations, however, were partly driven by the higher incidence of mTBI participants with both higher gamma activity and poorer cognition, suggesting that expansive upregulation of gamma has negative repercussions for cognition particularly in mTBI. This is the first human study to demonstrate abnormal resting-state gamma activity in mTBI. These novel findings suggest the possibility that abnormal gamma activities may be a proxy for GABA-ergic interneuron dysfunction and a promising neuroimaging marker of insidious mild head injuries.
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Concussão Encefálica/fisiopatologia , Encéfalo/fisiopatologia , Ritmo Gama , Adulto , Concussão Encefálica/psicologia , Humanos , Magnetoencefalografia , Masculino , Vias Neurais , Testes Neuropsicológicos , GuerraRESUMO
Visuospatial working memory impairments are common in Parkinson's disease (PD), yet the underlying neural mechanisms are poorly understood. The present study investigated abnormalities in context-dependent functional connectivity of working memory hubs in PD. Cognitively normal PD and control participants underwent fMRI while performing a visuospatial working memory task. To identify sources of dysfunction, distraction, and load-modulated connectivity were disentangled for encoding and retrieval phases of the task. Despite normal working memory performance in PD, two features of abnormal connectivity were observed, one due to a loss in normal context-related connectivity and another related to upregulated connectivity of hubs for which the controls did not exhibit context-dependent connectivity. During encoding, striatal-prefrontal coupling was lost in PD, both during distraction and high memory loads. However, long-range connectivity of prefrontal, medial temporal and occipital hubs was upregulated in a context-specific manner. Memory retrieval was characterized by different aberrant connectivity patterns, wherein precuneus connectivity was upregulated during distraction, whereas prefrontal couplings were lost as memory load approached capacity limits. Features of abnormal functional connectivity in PD had pathological and compensatory influences as they correlated with poorer working memory or better visuospatial skills. The results offer new insights into working memory-related signatures of aberrant cortico-cortical and corticostriatal functional connections, which may portend future declines in different facets of working memory.
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Memória de Curto Prazo , Vias Neurais/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/psicologia , Idoso , Bancos de Espécimes Biológicos , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Função Executiva , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Rememoração Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Córtex Pré-Frontal/diagnóstico por imagem , Desempenho Psicomotor , Percepção Espacial , Percepção VisualRESUMO
The hierarchical nature of language requires human brain to internally parse connected-speech and incrementally construct abstract linguistic structures. Recent research revealed multiple neural processing timescales underlying grammar-based configuration of linguistic hierarchies. However, little is known about where in the whole cerebral cortex such temporally scaled neural processes occur. This study used novel magnetoencephalography source imaging techniques combined with a unique language stimulation paradigm to segregate cortical maps synchronized to 3 levels of linguistic units (i.e., words, phrases, and sentences). Notably, distinct ensembles of cortical loci were identified to feature structures at different levels. The superior temporal gyrus was found to be involved in processing all 3 linguistic levels while distinct ensembles of other brain regions were recruited to encode each linguistic level. Neural activities in the right motor cortex only followed the rhythm of monosyllabic words which have clear acoustic boundaries, whereas the left anterior temporal lobe and the left inferior frontal gyrus were selectively recruited in processing phrases or sentences. Our results ground a multi-timescale hierarchical neural processing of speech in neuroanatomical reality with specific sets of cortices responsible for different levels of linguistic units.
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Idioma , Córtex Motor/fisiologia , Córtex Pré-Frontal/fisiologia , Percepção da Fala/fisiologia , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Córtex Motor/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Adulto JovemRESUMO
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.
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Concussão Encefálica/fisiopatologia , Concussão Encefálica/psicologia , Encéfalo/fisiopatologia , Distúrbios de Guerra/patologia , Distúrbios de Guerra/fisiopatologia , Memória de Curto Prazo/fisiologia , Adulto , Concussão Encefálica/etiologia , Ondas Encefálicas , Distúrbios de Guerra/complicações , Humanos , Magnetoencefalografia , Masculino , Testes Neuropsicológicos , VeteranosRESUMO
OBJECTIVE: To identify amygdalar volumetric differences associated with posttraumatic stress disorder (PTSD) in individuals with comorbid mild traumatic brain injury (mTBI) compared with those with mTBI-only and to examine the effects of intracranial volume (ICV) on amygdala volumetric measures. SETTING: Marine Corps Base and VA Healthcare System. PARTICIPANTS: A cohort of veterans and active-duty military personnel with combat-related mTBI (N = 89). DESIGN: Twenty-nine participants were identified with comorbid PTSD and mTBI. The remaining 60 formed the mTBI-only control group. Structural images of brains were obtained with a 1.5-T MRI scanner using a T1-weighted 3D-IR-FSPGR pulse sequence. Automatic segmentation was performed in Freesurfer. MAIN MEASURES: Amygdala volumes with/without normalizations to ICV. RESULTS: The comorbid mTBI/PTSD group had significantly larger amygdala volumes, when normalized to ICV, compared with the mTBI-only group. The right and left amygdala volumes after normalization to ICV were 0.122% ± 0.012% and 0.118% ± 0.011%, respectively, in the comorbid group compared with 0.115% ± 0.012% and 0.112% ± 0.009%, respectively, in the mTBI-only group (corrected P < .05). CONCLUSIONS: The ICV normalization analysis performed here may resolve previous literature discrepancies. This is an intriguing structural finding, given the role of the amygdala in the challenging neuroemotive symptoms witnessed in casualties of combat-related mTBI and PTSD.
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Tonsila do Cerebelo/patologia , Concussão Encefálica/patologia , Distúrbios de Guerra/patologia , Militares , Transtornos de Estresse Pós-Traumáticos/patologia , Veteranos , Adulto , Concussão Encefálica/psicologia , Estudos de Casos e Controles , Distúrbios de Guerra/complicações , Feminino , Humanos , Masculino , Tamanho do Órgão , Transtornos de Estresse Pós-Traumáticos/etiologiaRESUMO
BACKGROUND: Mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members, Veterans, and civilians. However, few treatments are available for mTBI, partially because the mechanism of persistent mTBI deficits is not fully understood. METHODS: We used magnetoencephalography (MEG) to investigate neuronal changes in individuals with mTBI following a passive neurofeedback-based treatment programme called IASIS. This programme involved applying low-intensity pulses using transcranial electrical stimulation (LIP-tES) with electroencephalography monitoring. Study participants included six individuals with mTBI and persistent post-concussive symptoms (PCS). MEG exams were performed at baseline and follow-up to evaluate the effect of IASIS on brain functioning. RESULTS: At the baseline MEG exam, all participants had abnormal slow-waves. In the follow-up MEG exam, the participants showed significantly reduced abnormal slow-waves with an average reduction of 53.6 ± 24.6% in slow-wave total score. The participants also showed significant reduction of PCS scores after IASIS treatment, with an average reduction of 52.76 ± 26.4% in PCS total score. CONCLUSIONS: The present study demonstrates, for the first time, the neuroimaging-based documentation of the effect of LIP-tES treatment on brain functioning in mTBI. The mechanisms of LIP-tES treatment are discussed, with an emphasis on LIP-tES's potentiation of the mTBI healing process.
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Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/terapia , Imageamento por Ressonância Magnética , Magnetoencefalografia , Estimulação Transcraniana por Corrente Contínua , Adulto , Eletroencefalografia , Feminino , Análise de Fourier , Humanos , Masculino , Testes Neuropsicológicos , Projetos Piloto , Síndrome Pós-Concussão/diagnóstico , Inquéritos e Questionários , VeteranosRESUMO
BACKGROUND: Increased temporal and frontal slow-wave delta (1-4 Hz) and theta (4-7 Hz) activities are the most consistent resting-state neural abnormalities reported in schizophrenia. The frontal lobe is associated with negative symptoms and cognitive abilities such as attention, with negative symptoms and impaired attention associated with poor functional capacity. AIMS: To establish whether frontal dysfunction, as indexed by slowing, would be associated with functional impairments. METHOD: Eyes-closed magnetoencephalography data were collected in 41 participants with schizophrenia and 37 healthy controls, and frequency-domain source imaging localised delta and theta activity. RESULTS: Elevated delta and theta activity in right frontal and right temporoparietal regions was observed in the schizophrenia v. CONTROL GROUP: In schizophrenia, right-frontal delta activity was uniquely associated with negative but not positive symptoms. In the full sample, increased right-frontal delta activity predicted poorer attention and functional capacity. CONCLUSIONS: Our findings suggest that treatment-associated decreases in slow-wave activity could be accompanied by improved functional outcome and thus better prognosis.
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Cognição , Função Executiva , Lobo Frontal/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Atenção , Estudos de Casos e Controles , Eletroencefalografia , Feminino , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de RegressãoRESUMO
OBJECTIVE: To examine whether cause, severity, and frequency of traumatic brain injury (TBI) increase risk of postdeployment tinnitus when accounting for comorbid posttraumatic stress disorder. DESIGN: Self-report and clinical assessments were done before and after an "index" deployment to Iraq or Afghanistan. SETTING, PARTICIPANTS, AND MEASURES: Assessments took place on Marine Corps bases in southern California and the VA San Diego Medical Center. Participants were 1647 active-duty enlisted Marine and Navy servicemen who completed pre- and postdeployment assessments of the Marine Resiliency Study. The main outcome was the presence of tinnitus at 3 months postdeployment. RESULTS: Predeployment TBI increased the likelihood of new-onset postdeployment tinnitus (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.28-2.70). Deployment-related TBIs increased the likelihood of postdeployment tinnitus (OR = 2.65; 95% CI, 1.19-5.89). Likelihood of new-onset postdeployment tinnitus was highest for those who were blast-exposed (OR = 2.93; 95% CI, 1.82-6.17), who reported moderate-severe TBI symptoms (OR = 2.22; 95% CI, 1.22-3.40), and who sustained multiple TBIs across study visits (OR = 2.27; 95% CI, 1.44-4.24). Posttraumatic stress disorder had no effect on tinnitus outcome. CONCLUSIONS: Participants who were blast-exposed, sustained multiple TBIs, and reported moderate-severe TBI symptoms were most at risk for new-onset tinnitus.
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Lesões Encefálicas/complicações , Militares , Zumbido/etiologia , Traumatismos por Explosões/complicações , Humanos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Estados Unidos , Guerra , Adulto JovemRESUMO
The brain's primary motor and primary somatosensory cortices are generally viewed as functionally distinct entities. Here we show by means of magnetoencephalography with a phantom-limb patient, that movement of the phantom hand leads to a change in the response of the primary somatosensory cortex to tactile stimulation. This change correlates with the described conscious perception and suggests a greater degree of functional unification between the primary motor and somatosensory cortices than is currently realized. We suggest that this may reflect the evolution of this part of the human brain, which is thought to have occurred from an undifferentiated sensorimotor cortex.
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Córtex Motor/fisiopatologia , Membro Fantasma/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Percepção do Tato/fisiologia , Adulto , Potenciais Somatossensoriais Evocados , Humanos , Magnetoencefalografia , Masculino , Estimulação FísicaRESUMO
The present study developed a fast MEG source imaging technique based on Fast Vector-based Spatio-Temporal Analysis using a L1-minimum-norm (Fast-VESTAL) and then used the method to obtain the source amplitude images of resting-state magnetoencephalography (MEG) signals for different frequency bands. The Fast-VESTAL technique consists of two steps. First, L1-minimum-norm MEG source images were obtained for the dominant spatial modes of sensor-waveform covariance matrix. Next, accurate source time-courses with millisecond temporal resolution were obtained using an inverse operator constructed from the spatial source images of Step 1. Using simulations, Fast-VESTAL's performance was assessed for its 1) ability to localize multiple correlated sources; 2) ability to faithfully recover source time-courses; 3) robustness to different SNR conditions including SNR with negative dB levels; 4) capability to handle correlated brain noise; and 5) statistical maps of MEG source images. An objective pre-whitening method was also developed and integrated with Fast-VESTAL to remove correlated brain noise. Fast-VESTAL's performance was then examined in the analysis of human median-nerve MEG responses. The results demonstrated that this method easily distinguished sources in the entire somatosensory network. Next, Fast-VESTAL was applied to obtain the first whole-head MEG source-amplitude images from resting-state signals in 41 healthy control subjects, for all standard frequency bands. Comparisons between resting-state MEG sources images and known neurophysiology were provided. Additionally, in simulations and cases with MEG human responses, the results obtained from using conventional beamformer technique were compared with those from Fast-VESTAL, which highlighted the beamformer's problems of signal leaking and distorted source time-courses.
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Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Magnetoencefalografia/métodos , Processamento de Sinais Assistido por Computador , Adulto , Algoritmos , Feminino , Humanos , Masculino , Descanso/fisiologia , Razão Sinal-RuídoRESUMO
Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual's distinct endophenotype.
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Inflamação , Lipopolissacarídeos , Humanos , Masculino , Feminino , Inflamação/induzido quimicamente , Adulto , Potenciais de Ação/efeitos dos fármacos , Adulto Jovem , Artérias Carótidas , Magnetometria/métodosRESUMO
Background: The substantial evidence that neural timing deficits are prevalent in developmental disorders, aging, and concussions resulting from a Traumatic Brain Injury (TBI) is presented. Objective: When these timing deficits are remediated using low-level movement-discrimination training, then high-level cognitive skills, including reading, attention, processing speed, problem solving, and working memory improve rapidly and effectively. Methods: In addition to the substantial evidence published previously, new evidence based on a neural correlate, MagnetoEncephalography physiological recordings, on an adult dyslexic, and neuropsychological tests on this dyslexic subject and an older adult were measured before and after 8-weeks of contrast sensitivity-based left-right movement-discrimination exercises were completed. Results: The neuropsychological tests found large improvements in reading, selective and sustained attention, processing speed, working memory, and problem-solving skills, never before found after such a short period of training. Moreover, these improvements were found 4 years later for older adult. Substantial MEG signal increases in visual Motion, Attention, and Memory/Executive Control Networks were observed following training on contrast sensitivity-based left-right movement-discrimination. Improving the function of magnocells using figure/ground movement-discrimination at both low and high levels in dorsal stream: (1) improved both feedforward and feedback pathways to modulate attention by enhancing coupled theta/gamma and alpha/gamma oscillations, (2) is adaptive, and (3) incorporated cycles of feedback and reward at multiple levels. Conclusion: What emerges from multiple studies is the essential role of timing deficits in the dorsal stream that are prevalent in developmental disorders like dyslexia, in aging, and following a TBI. Training visual dorsal stream function at low levels significantly improved high-level cognitive functions, including processing speed, selective and sustained attention, both auditory and visual working memory, problem solving, and reading fluency. A paradigm shift for treating cognitive impairments in developmental disorders, aging, and concussions is crucial. Remediating the neural timing deficits of low-level dorsal pathways, thereby improving both feedforward and feedback pathways, before cognitive exercises to improve specific cognitive skills provides the most rapid and effective methods to improve cognitive skills. Moreover, this adaptive training with substantial feedback shows cognitive transfer to tasks not trained on, significantly improving a person's quality of life rapidly and effectively.
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The objectives of this machine-learning (ML) resting-state magnetoencephalography (rs-MEG) study involving children with mild traumatic brain injury (mTBI) and orthopedic injury (OI) controls were to define a neural injury signature of mTBI and to delineate the pattern(s) of neural injury that determine behavioral recovery. Children ages 8-15 years with mTBI (n = 59) and OI (n = 39) from consecutive admissions to an emergency department were studied prospectively for parent-rated post-concussion symptoms (PCS) at: 1) baseline (average of 3 weeks post-injury) to measure pre-injury symptoms and also concurrent symptoms; and 2) at 3-months post-injury. rs-MEG was conducted at the baseline assessment. The ML algorithm predicted cases of mTBI versus OI with sensitivity of 95.5 ± 1.6% and specificity of 90.2 ± 2.7% at 3-weeks post-injury for the combined delta-gamma frequencies. The sensitivity and specificity were significantly better (p < 0.0001) for the combined delta-gamma frequencies compared with the delta-only and gamma-only frequencies. There were also spatial differences in rs-MEG activity between mTBI and OI groups in both delta and gamma bands in frontal and temporal lobe, as well as more widespread differences in the brain. The ML algorithm accounted for 84.5% of the variance in predicting recovery measured by PCS changes between 3 weeks and 3 months post-injury in the mTBI group, and this was significantly lower (p < 10-4) in the OI group (65.6%). Frontal lobe pole (higher) gamma activity was significantly (p < 0.001) associated with (worse) PCS recovery exclusively in the mTBI group. These findings demonstrate a neural injury signature of pediatric mTBI and patterns of mTBI-induced neural injury related to behavioral recovery.
Assuntos
Concussão Encefálica , Lesões Encefálicas , Síndrome Pós-Concussão , Humanos , Criança , Concussão Encefálica/diagnóstico , Concussão Encefálica/complicações , Magnetoencefalografia/métodos , Encéfalo , Síndrome Pós-Concussão/diagnóstico , Lesões Encefálicas/complicaçõesRESUMO
Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trails needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing M1 during ~1 minute recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-90 Hz) bands in 13 healthy participants (26 datasets) and two presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) and gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In both presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement related brain-muscle coupling above the movement frequency and its harmonics.
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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 because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI.
Assuntos
Lesões Encefálicas/diagnóstico , Lesões Encefálicas/fisiopatologia , Acidentes por Quedas , Acidentes de Trânsito , Adulto , Traumatismos em Atletas/complicações , Traumatismos por Explosões/complicações , Lesões Encefálicas/etiologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Magnetoencefalografia , Masculino , Processamento de Sinais Assistido por ComputadorRESUMO
The effects of neural activity on cerebral hemodynamics underlie human brain imaging with functional magnetic resonance imaging and positron emission tomography. However, the threshold and characteristics of the converse effects, wherein the cerebral hemodynamic and metabolic milieu influence neural activity, remain unclear. We tested whether mild hypercapnia (5% CO2 ) decreases the magnetoencephalogram response to auditory pattern recognition and visual semantic tasks. Hypercapnia induced statistically significant decreases in event-related fields without affecting behavioral performance. Decreases were observed in early sensory components in both auditory and visual modalities as well as later cognitive components related to memory and language. Effects were distributed across cortical regions. Decreases were comparable in evoked versus spontaneous spectral power. Hypercapnia is commonly used with hemodynamic models to calibrate the blood oxygenation level-dependent response. Modifying model assumptions to incorporate the current findings produce a modest but measurable decrease in the estimated cerebral metabolic rate for oxygen change with activation. Because under normal conditions, low cerebral pH would arise when bloodflow is unable to keep pace with neuronal activity, the cortical depression observed here may reflect a homeostatic mechanism by which neuronal activity is adjusted to a level that can be sustained by available bloodflow. Animal studies suggest that these effects may be mediated by pH-modulating presynaptic adenosine receptors. Although the data is not clear, comparable changes in cortical pH to those induced here may occur during sleep apnea, sleep, and exercise. If so, these results suggest that such activities may in turn have generalized depressive effects on cortical activity.
Assuntos
Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiopatologia , Hemodinâmica/fisiologia , Hipercapnia/fisiopatologia , Adulto , Percepção Auditiva/fisiologia , Circulação Cerebrovascular/fisiologia , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Visuais/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Magnetocardiografia , Masculino , Percepção Visual/fisiologia , Adulto JovemRESUMO
Background: Spatial cognition deteriorates in Parkinson's disease (PD), but the neural substrates are not understood, despite the risk for future dementia. It is also unclear whether deteriorating spatial cognition relates to changes in other cognitive domains or contributes to motor dysfunction. Objective: This study aimed to identify functional connectivity abnormalities in cognitively normal PD (PDCN) in regions that support spatial cognition to determine their relationship to interfacing cognitive functions and motor disability, and to determine if they predict cognitive and motor progression 2 years later in a PDCN subsample. Methods: Sixty-three PDCN and 43 controls underwent functional MRI while judging whether pictures, rotated at various angles, depicted the left or right hand. The task activates systems that respond to increases in rotation angle, a proxy for visuospatial difficulty. Angle-modulated functional connectivity was analyzed for frontal cortex, posterior cortex, and basal ganglia regions. Results: Two aberrant connectivity patterns were found in PDCN, which were condensed into principal components that characterized the strength and topology of angle-modulated connectivity. One topology related to a marked failure to amplify frontal, posterior, and basal ganglia connectivity with other brain areas as visuospatial demands increased, unlike the control group (control features). Another topology related to functional reorganization whereby regional connectivity was strengthened with brain areas not recruited by the control group (PDCN features). Functional topologies correlated with diverse cognitive domains at baseline, underscoring their influences on spatial cognition. In PDCN, expression of topologies that were control features predicted greater cognitive progression longitudinally, suggesting inefficient communications within circuitry normally recruited to handle spatial demands. Conversely, stronger expression of topologies that were PDCN features predicted less longitudinal cognitive decline, suggesting functional reorganization was compensatory. Parieto-occipital topologies (control features) had different prognostic implications for longitudinal changes in motor disability. Expression of one topology predicted less motor decline, whereas expression of another predicted increased postural instability and gait disturbance (PIGD) feature severity. Concurrently, greater longitudinal decline in spatial cognition predicted greater motor and PIGD feature progression, suggesting deterioration in shared substrates. Conclusion: These novel discoveries elucidate functional mechanisms of visuospatial cognition in PDCN, which foreshadow future cognitive and motor disability.