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1.
Schizophr Bull ; 48(6): 1306-1317, 2022 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-35988022

RESUMEN

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) and bipolar disorder (BD) share genetic risk factors, yet patients display differential levels of cognitive impairment. We hypothesized a genome-transcriptome-functional connectivity (frontoparietal)-cognition pathway linked to SZ-versus-BD differences, and conducted a multiscale study to delineate this pathway. STUDY DESIGNS: Large genome-wide studies provided single nucleotide polymorphisms (SNPs) conferring more risk for SZ than BD, and we identified their regulated genes, namely SZ-biased SNPs and genes. We then (a) computed the polygenic risk score for SZ (PRSSZ) of SZ-biased SNPs and examined its associations with imaging-based frontoparietal functional connectivity (FC) and cognitive performances; (b) examined the spatial correlation between ex vivo postmortem expressions of SZ-biased genes and in vivo, SZ-related FC disruptions across frontoparietal regions; (c) investigated SZ-versus-BD differences in frontoparietal FC; and (d) assessed the associations of frontoparietal FC with cognitive performances. STUDY RESULTS: PRSSZ of SZ-biased SNPs was significantly associated with frontoparietal FC and working memory test scores. SZ-biased genes' expressions significantly correlated with SZ-versus-BD differences in FC across frontoparietal regions. SZ patients showed more reductions in frontoparietal FC than BD patients compared to controls. Frontoparietal FC was significantly associated with test scores of multiple cognitive domains including working memory, and with the composite scores of all cognitive domains. CONCLUSIONS: Collectively, these multiscale findings support the hypothesis that SZ-biased genetic risk, through transcriptome regulation, is linked to frontoparietal dysconnectivity, which in turn contributes to differential cognitive deficits in SZ-versus BD, suggesting that potential biomarkers for more precise patient stratification and treatment.


Asunto(s)
Trastorno Bipolar , Trastornos del Conocimiento , Esquizofrenia , Humanos , Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/genética , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/genética , Transcriptoma , Cognición
2.
Schizophr Res ; 229: 12-21, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33607607

RESUMEN

Patients with psychotic spectrum disorders (PSD) exhibit similar patterns of atrophy and microstructural changes that may be associated with common symptomatology (e.g., symptom burden and/or cognitive impairment). Gray matter concentration values (proxy for atrophy), fractional anisotropy (FA), mean diffusivity (MD), intracellular neurite density (Vic) and isotropic diffusion volume (Viso) measures were therefore compared in 150 PSD (schizophrenia, schizoaffective disorder, and bipolar disorder Type I) and 63 healthy controls (HC). Additional analyses evaluated whether regions showing atrophy and/or microstructure abnormalities were better explained by DSM diagnoses, symptom burden or cognitive dysfunction. PSD exhibited increased atrophy within bilateral medial temporal lobes and subcortical structures. Gray matter along the left lateral sulcus showed evidence of increased atrophy and MD. Increased MD was also observed in homotopic fronto-temporal regions, suggesting it may serve as a precursor to atrophic changes. Global cognitive dysfunction, rather than DSM diagnoses or psychotic symptom burden, was the best predictor of increased gray matter MD. Regions of decreased FA (i.e., left frontal gray and white matter) and Vic (i.e., frontal and temporal regions and along central sulcus) were also observed for PSD, but were neither spatially concurrent with atrophic regions nor associated with clinical symptoms. Evidence of expanding microstructural spaces in gray matter demonstrated the greatest spatial overlap with current and potentially future regions of atrophy, and was associated with cognitive deficits. These results suggest that this particular structural abnormality could potentially underlie global cognitive impairment that spans traditional diagnostic categories.


Asunto(s)
Trastornos Psicóticos , Sustancia Blanca , Atrofia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología
3.
J Psychiatry Neurosci ; 45(6): 430-440, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32869961

RESUMEN

Background: Functional underpinnings of cognitive control deficits in unbiased samples (i.e., all comers) of patients with psychotic spectrum disorders (PSD) remain actively debated. While many studies suggest hypofrontality in the lateral prefrontal cortex (PFC) and greater deficits during proactive relative to reactive control, few have examined the full hemodynamic response. Methods: Patients with PSD (n = 154) and healthy controls (n = 65) performed the AX continuous performance task (AX-CPT) during rapid (460 ms) functional neuroimaging and underwent full clinical characterization. Results: Behavioural results indicated generalized cognitive deficits (slower and less accurate) across proactive and reactive control conditions in patients with PSD relative to healthy controls. We observed a delayed/prolonged neural response in the left dorsolateral PFC, the sensorimotor cortex and the superior parietal lobe during proactive control for patients with PSD. These proactive hemodynamic abnormalities were better explained by negative rather than by positive symptoms or by traditional diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR), with subsequent simulations unequivocally demonstrating how these abnormalities could be erroneously interpreted as hypoactivation. Conversely, true hypoactivity, unassociated with clinical symptoms or DSM-IV-TR diagnoses, was observed within the ventrolateral PFC during reactive control. Limitations: In spite of guidance for AX-CPT use in neuroimaging studies, one-third of patients with PSD could not perform the task above chance and were more clinically impaired. Conclusion: Current findings question the utility of the AX-CPT for neuroimaging-based appraisal of cognitive control across the full spectrum of patients with PSD. Previously reported lateral PFC "hypoactivity" during proactive control may be more indicative of a delayed/prolonged neural response, important for rehabilitative purposes. Negative symptoms may better explain certain behavioural and hemodynamic abnormalities in patients with PSD relative to DSM-IV-TR diagnoses.


Asunto(s)
Función Ejecutiva/fisiología , Neuroimagen Funcional/normas , Lóbulo Parietal/fisiopatología , Corteza Prefrontal/fisiopatología , Desempeño Psicomotor/fisiología , Trastornos Psicóticos/fisiopatología , Corteza Sensoriomotora/fisiopatología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Lóbulo Parietal/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Trastornos Psicóticos/diagnóstico por imagen , Corteza Sensoriomotora/diagnóstico por imagen , Adulto Joven
4.
Cortex ; 129: 314-328, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32554227

RESUMEN

Sensorimotor synchronization (SMS) is frequently dependent on coordination of excitatory and inhibitory activity across hemispheres, as well as the cognitive control over environmental distractors. However, the timing (motor planning versus execution) and cortical regions involved in these processes remain actively debated. Functional magnetic resonance imaging data were therefore analyzed from 34 strongly right-handed healthy adults performing a cued (to initiate motor planning) SMS task with either their right or left hand (motor execution phase) based on spatially congruent or incongruent visual stimuli. Behavioral effects of incongruent stimuli were limited to the first stimulus. Functionally, greater activation was observed in left sensorimotor cortex (SMC) and right cerebellar Lobule V for congruent versus incongruent stimuli. A negative blood-oxygen level dependent response, a putative marker of neural inhibition, was present in bilateral SMC, right supplemental motor area (SMA) and bilateral cerebellar Lobule V during the motor planning, but not execution phase. The magnitude of the inhibitory response was greater in right cortical regions and cerebellar Lobule V. Homologue connectivity was associated with inhibitory activity in the right SMA, suggesting that individual differences in intrinsic connectivity may mediate transcallosal inhibition. In summary, results suggest increased inhibition (i.e., greater negative BOLD response) within the right relative to left hemisphere, which was released once motor programs were executed. Both task and intrinsic functional connectivity results highlight a critical role of the left SMA in interhemispheric inhibition and motor planning.


Asunto(s)
Corteza Motora , Adulto , Cerebelo , Señales (Psicología) , Mano , Humanos , Imagen por Resonancia Magnética , Desempeño Psicomotor
5.
J Head Trauma Rehabil ; 35(4): 270-278, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32108710

RESUMEN

OBJECTIVE: To evaluate diagnostic/prognostic implications of neurosensory testing during the subacute stage in patients with pediatric mild traumatic brain injury (pmTBI). SETTING: Recruitment from pediatric emergency department and urgent care clinics, assessment in a controlled environment. PARTICIPANTS: In total, 146 pmTBI patients evaluated 7.4 ± 2.3 days and approximately 4 months postinjury; 104 age/sex-matched healthy controls (HCs) at equivalent time points. DESIGN: Prospective cohort study. MAIN MEASURES: Neurosensory examination based on sequence of 10 established tests of vestibular-ocular, oculomotor, vestibulospinal, and visual functioning. RESULTS: The amount of symptom provocation (positive change from pretest symptomatology) was significantly increased in pmTBI relative to HCs on every subtest 1 week postinjury, as were deficits in monocular accommodative amplitude and King-Devick Test errors. However, symptom provocation did not meaningfully alter diagnostic sensitivity/specificity relative to more easily obtained pretest symptom ratings. Evidence of clinically significant symptom provocation 1 week postinjury improved sensitivity (Δ = +12.9%) of identifying patients with persistent postconcussive symptoms 4 months postinjury on an independent symptom measure. CONCLUSIONS: The diagnostic sensitivity/specificity of neurosensory testing in acutely concussed youth may be limited at 1 week postinjury as a function of natural recovery occurring in most emergency department cohorts. Neurosensory screening may have greater utility for identifying patients who experience delayed recovery.


Asunto(s)
Conmoción Encefálica , Síndrome Posconmocional , Adolescente , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Síndrome Posconmocional/diagnóstico , Estudios Prospectivos , Calidad de Vida
6.
Neurology ; 94(3): e241-e253, 2020 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-31645467

RESUMEN

OBJECTIVE: The nosology for classifying structural MRI findings following pediatric mild traumatic brain injury (pmTBI) remains actively debated. Radiologic common data elements (rCDE) were developed to standardize reporting in research settings. However, some rCDE are more specific to trauma (probable rCDE). Other more recently proposed rCDE have multiple etiologies (possible rCDE), and may therefore be more common in all children. Independent cohorts of patients with pmTBI and controls were therefore recruited from multiple sites (New Mexico and Ohio) to test the dual hypothesis of a higher incidence of probable rCDE (pmTBI > controls) vs similar rates of possible rCDE on structural MRI. METHODS: Patients with subacute pmTBI (n = 287), matched healthy controls (HC; n = 106), and orthopedically injured (OI; n = 71) patients underwent imaging approximately 1 week postinjury and were followed for 3-4 months. RESULTS: Probable rCDE were specific to pmTBI, occurring in 4%-5% of each sample, rates consistent with previous large-scale CT studies. In contrast, prevalence rates for incidental findings and possible rCDE were similar across groups (pmTBI vs OI vs HC). The prevalence of possible rCDE was also the only finding that varied as a function of site. Possible rCDE and incidental findings were not associated with postconcussive symptomatology or quality of life 3-4 months postinjury. CONCLUSION: Collectively, current findings question the trauma-related specificity of certain rCDE, as well how these rCDE are radiologically interpreted. Refinement of rCDE in the context of pmTBI may be warranted, especially as diagnostic schema are evolving to stratify patients with structural MRI abnormalities as having a moderate injury.


Asunto(s)
Conmoción Encefálica/clasificación , Conmoción Encefálica/diagnóstico por imagen , Conmoción Encefálica/patología , Interpretación de Imagen Asistida por Computador/normas , Imagen por Resonancia Magnética/normas , Adolescente , Niño , Elementos de Datos Comunes , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino
7.
Hum Brain Mapp ; 40(13): 3843-3859, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31119818

RESUMEN

It has been known for decades that head motion/other artifacts affect the blood oxygen level-dependent signal. Recent recommendations predominantly focus on denoising resting state data, which may not apply to task data due to the different statistical relationships that exist between signal and noise sources. Several blind-source denoising strategies (FIX and AROMA) and more standard motion parameter (MP) regression (0, 12, or 24 parameters) analyses were therefore compared across four sets of event-related functional magnetic resonance imaging (erfMRI) and block-design (bdfMRI) datasets collected with multiband 32- (repetition time [TR] = 460 ms) or older 12-channel (TR = 2,000 ms) head coils. The amount of motion varied across coil designs and task types. Quality control plots indicated small to moderate relationships between head motion estimates and percent signal change in both signal and noise regions. Blind-source denoising strategies eliminated signal as well as noise relative to MP24 regression; however, the undesired effects on signal depended both on algorithm (FIX > AROMA) and design (bdfMRI > erfMRI). Moreover, in contrast to previous results, there were minimal differences between MP12/24 and MP0 pipelines in both erfMRI and bdfMRI designs. MP12/24 pipelines were detrimental for a task with both longer block length (30 ± 5 s) and higher correlations between head MPs and design matrix. In summary, current results suggest that there does not appear to be a single denoising approach that is appropriate for all fMRI designs. However, even nonaggressive blind-source denoising approaches appear to remove signal as well as noise from task-related data at individual subject and group levels.


Asunto(s)
Artefactos , Encéfalo/fisiología , Neuroimagen Funcional/métodos , Movimientos de la Cabeza , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Femenino , Neuroimagen Funcional/normas , Humanos , Procesamiento de Imagen Asistido por Computador/normas , Imagen por Resonancia Magnética/normas , Masculino , Reconocimiento Visual de Modelos/fisiología , Desempeño Psicomotor/fisiología , Proyectos de Investigación , Adulto Joven
8.
Schizophr Res ; 208: 344-352, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30711315

RESUMEN

BACKGROUND: Patients with psychotic spectrum disorders share overlapping clinical/biological features, making it often difficult to separate them into a discrete nosology (i.e., Diagnostic and Statistical Manual of Mental Disorders [DSM]). METHODS: The current study investigated whether a continuum classification scheme based on symptom burden would improve conceptualizations for cognitive and real-world dysfunction relative to traditional DSM nosology. Two independent samples (New Mexico [NM] and Bipolar and Schizophrenia Network on Intermediate Phenotypes [B-SNIP]) of patients with schizophrenia (NM: N = 93; B-SNIP: N = 236), bipolar disorder Type I (NM: N = 42; B-SNIP: N = 195) or schizoaffective disorder (NM: N = 15; B-SNIP: N = 148) and matched healthy controls (NM: N = 64; B-SNIP: N = 717) were examined. Linear regressions examined how variance differed as a function of classification scheme (DSM diagnosis, negative and positive symptom burden, or a three-cluster solution based on symptom burden). RESULTS: Symptom-based classification schemes (continuous and clustered) accounted for a significantly larger portion of captured variance of real-world functioning relative to DSM diagnoses across both samples. The symptom-based classification schemes accounted for large percentages of variance for general cognitive ability and cognitive domains in the NM sample. However, in the B-SNIP sample, symptom-based classification schemes accounted for roughly equivalent variance as DSM diagnoses. A potential mediating variable across samples was the strength of the relationship between negative symptoms and impaired cognition. CONCLUSIONS: Current results support suggestions that a continuum perspective of psychopathology may be more powerful for explaining real-world functioning than the DSM diagnostic nosology, whereas results for cognitive dysfunction were sample dependent.


Asunto(s)
Trastornos del Conocimiento/psicología , Inteligencia Emocional , Trastornos Psicóticos/psicología , Evaluación de Síntomas/psicología , Adolescente , Adulto , Trastorno Bipolar/clasificación , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/psicología , Trastornos del Conocimiento/clasificación , Trastornos del Conocimiento/diagnóstico , Costo de Enfermedad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Inteligencia Emocional/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fenotipo , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/clasificación , Trastornos Psicóticos/diagnóstico , Evaluación de Síntomas/clasificación , Adulto Joven
9.
Schizophr Bull ; 45(1): 222-232, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29474680

RESUMEN

Genetic factors are known to influence both risk for schizophrenia (SZ) and variation in brain structure. A pressing question is whether the genetic underpinnings of brain phenotype and the disorder overlap. Using multivariate analytic methods and focusing on 1,402 common single-nucleotide polymorphisms (SNPs) mapped from the Psychiatric Genomics Consortium (PGC) 108 regions, in 777 discovery samples, we identified 39 SNPs to be significantly associated with SZ-discriminating gray matter volume (GMV) reduction in inferior parietal and superior temporal regions. The findings were replicated in 609 independent samples. These 39 SNPs in chr6:28308034-28684183 (6p22.1), the most significant SZ-risk region reported by PGC, showed regulatory effects on both DNA methylation and gene expression of postmortem brain tissue and saliva. Furthermore, the regulated methylation site and gene showed significantly different levels of methylation and expression in the prefrontal cortex between cases and controls. In addition, for one regulated methylation site we observed a significant in vivo methylation-GMV association in saliva, suggesting a potential SNP-methylation-GMV pathway. Notably, the risk alleles inferred for GMV reduction from in vivo imaging are all consistent with the risk alleles for SZ inferred from postmortem data. Collectively, we provide evidence for shared genetic risk of SZ and regional GMV reduction in 6p22.1 and demonstrate potential molecular mechanisms that may drive the observed in vivo associations. This study motivates dissecting SZ-risk variants to better understand their associations with focal brain phenotypes and the complex pathophysiology of the illness.


Asunto(s)
Cromosomas Humanos Par 6/genética , Predisposición Genética a la Enfermedad/genética , Sustancia Gris/patología , Lóbulo Parietal/patología , Corteza Prefrontal/patología , Trastornos Psicóticos/genética , Trastornos Psicóticos/patología , Esquizofrenia/genética , Esquizofrenia/patología , Adolescente , Adulto , Femenino , Estudios de Asociación Genética , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Parietal/diagnóstico por imagen , Polimorfismo de Nucleótido Simple , Corteza Prefrontal/diagnóstico por imagen , Trastornos Psicóticos/diagnóstico por imagen , Riesgo , Esquizofrenia/diagnóstico por imagen , Adulto Joven
10.
Schizophr Bull ; 45(3): 552-561, 2019 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-29939338

RESUMEN

Inhibitory failure represents a core dysfunction in patients with schizophrenia (SP), which has predominantly been tested in the literature using reactive (ie, altering behavior after a stimulus) rather than proactive (ie, purposefully changing behavior before a stimulus) response inhibition tasks. The current study replicates/extends our previous findings of SP exhibiting sensorimotor cortex (SMC) hyperactivity and connectivity abnormalities in independent samples of patients and controls. Specifically, 49 clinically well-characterized SP and 54 matched healthy controls (HC) performed a proactive response inhibition task while undergoing functional magnetic resonance imaging and resting-state data collection. Results indicated that the majority of SP (84%) and HC (88%) successfully inhibited all overt motor responses following a cue, eliminating behavioral confounds frequently present in this population. Observations of left SMC hyperactivity during proactive response inhibition, reduced cortical connectivity with left SMC, and increased connectivity between left SMC and ventrolateral thalamus were replicated for SP relative to HC in the current study. Similarly, negative symptoms (eg, motor retardation) were again associated with SMC functional and connectivity abnormalities. In contrast, findings of a negative blood oxygenation level-dependent response in the SMC of HC did not replicate. Collectively, current and previous findings suggest that SMC connectivity abnormalities may be more robust relative to evoked hemodynamic signals during proactive response inhibition. In addition, there is strong support that these SMC abnormalities are a key component of SP pathology, along with dysfunction within other sensory cortices, and may be associated with certain clinical deficits such as negative symptoms.


Asunto(s)
Atención/fisiología , Encéfalo/fisiopatología , Conectoma , Red Nerviosa/fisiopatología , Inhibición Proactiva , Desempeño Psicomotor/fisiología , Esquizofrenia/fisiopatología , Corteza Sensoriomotora/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Esquizofrenia/diagnóstico por imagen , Corteza Sensoriomotora/diagnóstico por imagen , Adulto Joven
11.
Hum Brain Mapp ; 40(3): 955-966, 2019 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-30407681

RESUMEN

The role of ventral versus dorsolateral prefrontal regions in instantiating proactive and reactive cognitive control remains actively debated, with few studies parsing cue versus probe-related activity. Rapid sampling (460 ms), long cue-probe delays, and advanced analytic techniques (deconvolution) were therefore used to quantify the magnitude and variability of neural responses during the AX Continuous Performance Test (AX-CPT; N = 46) in humans. Behavioral results indicated slower reaction times during reactive cognitive control (AY trials) in conjunction with decreased accuracy and increased variability for proactive cognitive control (BX trials). The anterior insula/ventrolateral prefrontal cortex (aI/VLPFC) was commonly activated across comparisons of both proactive and reactive cognitive control. In contrast, activity within the dorsomedial and dorsolateral prefrontal cortex was limited to reactive cognitive control. The instantiation of proactive cognitive control during the probe period was also associated with sparse neural activation relative to baseline, potentially as a result of the high degree of neural and behavioral variability observed across individuals. Specifically, the variability of the hemodynamic response function (HRF) within motor circuitry increased after the presentation of B relative to A cues (i.e., late in HRF) and persisted throughout the B probe period. Finally, increased activation of right aI/VLPFC during the cue period was associated with decreased motor circuit activity during BX probes, suggesting a possible role for the aI/VLPFC in proactive suppression of neural responses. Considered collectively, current results highlight the flexible role of the VLPFC in implementing cognitive control during the AX-CPT task but suggest large individual differences in proactive cognitive control strategies.


Asunto(s)
Cognición/fisiología , Corteza Prefrontal/fisiología , Tiempo de Reacción/fisiología , Adulto , Imagen Eco-Planar/métodos , Femenino , Humanos , Masculino
12.
Neurosci Biobehav Rev ; 94: 149-165, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30098989

RESUMEN

There is growing public concern about neurodegenerative changes (e.g., Chronic Traumatic Encephalopathy) that may occur chronically following clinically apparent and clinically silent (i.e., sub-concussive blows) pediatric mild traumatic brain injury (pmTBI). However, there are currently no biomarkers that clinicians can use to objectively diagnose patients or predict those who may struggle to recover. Non-invasive neuroimaging, electrophysiological and neuromodulation biomarkers have promise for providing evidence of the so-called "invisible wounds" of pmTBI. Our systematic review, however, belies that notion, identifying a relative paucity of high-quality, clinically impactful, diagnostic or prognostic biomarker studies in the sub-acute injury phase (36 studies on unique samples in 28 years), with the majority focusing on adolescent pmTBI. Ultimately, well-powered longitudinal studies with appropriate control groups, as well as standardized and clearly-defined inclusion criteria (time post-injury, injury severity and past history) are needed to truly understand the complex pathophysiology that is hypothesized (i.e., still needs to be determined) to exist during the acute and sub-acute stages of pmTBI and may underlie post-concussive symptoms.


Asunto(s)
Conmoción Encefálica/diagnóstico por imagen , Conmoción Encefálica/metabolismo , Animales , Biomarcadores/metabolismo , Niño , Humanos , Metaanálisis como Asunto
13.
Biol Psychiatry ; 84(9): 675-683, 2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-29921417

RESUMEN

BACKGROUND: Disrupted proactive cognitive control, a form of early selection and active goal maintenance, is hypothesized to underlie the broad cognitive deficits observed in patients with schizophrenia (SPs). Current research suggests that the disrupted activation within and connectivity between regions of the cognitive control network contribute to disrupted proactive cognitive control; however, no study has examined these mechanisms using an AX Continuous Performance Test task in schizophrenia. METHODS: Twenty-six SPs (17 male subjects; mean age 34.46 ± 8.77 years) and 28 healthy control participants (HCs; 16 male subjects; mean age 31.43 ± 7.23 years) underwent an electroencephalogram while performing the AX Continuous Performance Test. To examine the extent of activation and level of connectivity within the cognitive control network, power, intertrial phase clustering, and intersite phase clustering metrics were calculated and analyzed. RESULTS: SPs exhibited expected general decrements in behavioral performance relative to HCs and a more selective deficit in conditions requiring proactive cognitive control. Additionally, SPs exhibited deficits in midline theta power and connectivity during proactive cognitive control trials. Specifically, HCs exhibited significantly greater theta power for B cues relative to A cues, whereas SPs exhibited no significant differences between A- and B-cue theta power. Additionally, differential theta connectivity patterns were observed in SPs and HCs. Behavioral measures of proactive cognitive control predicted functional outcomes in SPs. CONCLUSIONS: This study suggests that low-frequency midline theta activity is selectively disrupted during proactive cognitive control in SPs. The disrupted midline theta activity may reflect a failure of SPs to proactively recruit cognitive control processes.


Asunto(s)
Cognición/fisiología , Lóbulo Frontal/fisiopatología , Esquizofrenia/fisiopatología , Ritmo Teta/fisiología , Adulto , Estudios de Casos y Controles , Señales (Psicología) , Electroencefalografía , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Tiempo de Reacción , Adulto Joven
14.
Artículo en Inglés | MEDLINE | ID: mdl-29486871

RESUMEN

BACKGROUND: Chronic alcohol use disorders (AUDs) and traumatic brain injury (TBI) are highly comorbid and share commonly affected neuronal substrates (i.e., prefrontal cortex, limbic system, and cerebellum). However, no studies have examined how combined physical trauma and heavy drinking affect neurocircuitry relative to heavy drinking alone. METHODS: The current study investigated whether comorbid AUDs and mild or moderate TBI (AUDs+TBI) would negatively affect maladaptive drinking behaviors (n = 90 AUDs+TBI; n = 62 AUDs) as well as brain structure (i.e., increased atrophy; n = 62 AUDs+TBI; n = 44 AUDs) and function (i.e., activation during gustatory cue reactivity; n = 55 AUDs+TBI; n = 37 AUDs) relative to AUDs alone. RESULTS: Participants reported a much higher incidence of trauma (59.2%) compared with the general population. There were no differences in demographic and clinical measures between groups, suggesting that they were well matched. Although maladaptive drinking behaviors tended to be worse for the AUDs+TBI group, effect sizes were small and not statistically significant. Increased alcohol-cue reactivity was observed in bilateral anterior insula and orbitofrontal cortex, anterior cingulate cortex, medial prefrontal cortex, posterior cingulate cortex, dorsal striatum, thalamus, brainstem, and cerebellum across both groups relative to a carefully matched appetitive control. However, there were no significant differences in structural integrity or functional activation between AUDs+TBI and AUDs participants, even when controlling for AUD severity. CONCLUSIONS: Current results indicate that a combined history of mild or moderate TBI was not sufficient to alter drinking behaviors and/or underlying neurocircuitry at detectable levels relative to heavy drinking alone. Future studies should examine the potential long-term effects of combined alcohol and trauma on brain functioning.


Asunto(s)
Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/psicología , Lesiones Traumáticas del Encéfalo/psicología , Encéfalo/diagnóstico por imagen , Adulto , Alcoholismo/complicaciones , Alcoholismo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Señales (Psicología) , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
15.
Front Hum Neurosci ; 11: 293, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28634448

RESUMEN

Successful adaptive behavior relies on the ability to automatically (bottom-up) orient attention to different locations in the environment. This results in a biphasic pattern in which reaction times (RT) are faster for stimuli that occur in the same spatial location (valid) for the first few hundred milliseconds, which is termed facilitation. This is followed by faster RT for stimuli that appear in novel locations (invalid) after longer delays, termed inhibition of return. The neuronal areas and networks involved in the transition between states of facilitation and inhibition remain poorly understood, especially for auditory stimuli. Functional magnetic resonance imaging (fMRI) data were therefore collected in a large sample of healthy volunteers (N = 52) at four separate auditory stimulus onset asynchronies (SOAs; 200, 400, 600, and 800 ms). Behavioral results indicated that facilitation (valid RT < invalid RT) occurred at the 200 ms SOA, with inhibition of return (valid RT > invalid RT) present at the three longer SOAs. fMRI results showed several brain areas varying their activation as a function of SOA, including bilateral superior temporal gyrus, anterior thalamus, cuneus, dorsal anterior cingulate gyrus, and right ventrolateral prefrontal cortex (VLPFC)/anterior insula. Right VLPFC was active during a behavioral state of facilitation, and its activation (invalid - valid trials) further correlated with behavioral reorienting at the 200 ms delay. These results suggest that right VLPFC plays a critical role when auditory attention must be quickly deployed or redeployed, demanding heightened cognitive and inhibitory control. In contrast to previous work, the ventral and dorsal frontoparietal attention networks were both active during valid and invalid trials across SOAs. These results suggest that the dorsal and ventral networks may not be as specialized during bottom-up auditory orienting as has been previously reported during visual orienting.

16.
Curr Sports Med Rep ; 16(1): 30-35, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28067738

RESUMEN

There is evidence that repetitive mild traumatic brain injury leads to specific patterns of neuropathological findings, labeled chronic traumatic encephalopathy (CTE). However, questions remain about whether these neuropathological changes produce changes in behavior, cognition, and emotional status that are associated with a unique neuropsychiatric profile that can be assessed using currently available clinical tools. Our review of the literature indicates that insufficient evidence currently exists to suggest a distinct neuropsychiatric profile for CTE. Major limitations to the field presently include the relatively nascent nature of the topic, reliance on retrospective next-of-kin reporting, the lack of prospective studies, and similarities in neuropsychiatric symptoms between CTE, other neurodegenerative disorders and forms of psychopathology. Clinicians and researchers alike have a responsibility to adopt a cautious and balanced approach for antemortem assessments to minimize the potential unintended negative consequences of both overdiagnosing and underdiagnosing a clinical entity that has yet to be clearly established.


Asunto(s)
Traumatismos en Atletas/diagnóstico , Traumatismos en Atletas/psicología , Encefalopatía Traumática Crónica/diagnóstico , Encefalopatía Traumática Crónica/psicología , Pruebas Neuropsicológicas , Evaluación de Síntomas/métodos , Diagnóstico Diferencial , Técnicas de Diagnóstico Neurológico , Medicina Basada en la Evidencia , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
17.
Cereb Cortex ; 27(5): 2831-2840, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-27166168

RESUMEN

Parsing multisensory information from a complex external environment is a fundamental skill for all organisms. However, different organizational schemes currently exist for how multisensory information is processed in human (supramodal; organized by cognitive demands) versus primate (organized by modality/cognitive demands) lateral prefrontal cortex (LPFC). Functional magnetic resonance imaging results from a large cohort of healthy controls (N = 64; Experiment 1) revealed a rostral-caudal stratification of LPFC for auditory versus visual attention during an audio-visual Stroop task. The stratification existed in spite of behavioral and functional evidence of increased interference from visual distractors. Increased functional connectivity was also observed between rostral LPFC and auditory cortex across independent samples (Experiments 2 and 3) and multiple methodologies. In contrast, the caudal LPFC was preferentially activated during visual attention but functioned in a supramodal capacity for resolving multisensory conflict. The caudal LPFC also did not exhibit increased connectivity with visual cortices. Collectively, these findings closely mirror previous nonhuman primate studies suggesting that visual attention relies on flexible use of a supramodal cognitive control network in caudal LPFC whereas rostral LPFC is specialized for directing attention to auditory inputs (i.e., human auditory fields).


Asunto(s)
Vías Aferentes/fisiología , Atención , Percepción Auditiva/fisiología , Cognición/fisiología , Corteza Prefrontal/fisiología , Percepción Visual/fisiología , Estimulación Acústica , Adolescente , Adulto , Vías Aferentes/diagnóstico por imagen , Análisis de Varianza , Mapeo Encefálico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxígeno , Estimulación Luminosa , Corteza Prefrontal/diagnóstico por imagen , Adulto Joven
18.
Brain Imaging Behav ; 11(3): 698-711, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27071950

RESUMEN

Although diffusion magnetic resonance imaging (dMRI) has been widely used to characterize the effects of repetitive mild traumatic brain injury (rmTBI), to date no studies have investigated how novel geometric models of microstructure relate to more typical diffusion tensor imaging (DTI) sequences. Moreover, few studies have evaluated the sensitivity of different registration pipelines (non-linear, linear and tract-based spatial statistics) for detecting dMRI abnormalities in clinical populations. Results from single-subject analyses in healthy controls (HC) indicated a strong negative relationship between fractional anisotropy (FA) and orientation dispersion index (ODI) in both white and gray matter. Equally important, only moderate relationships existed between all other estimates of free/intracellular water volume fractions and more traditional DTI metrics (FA, mean, axial and radial diffusivity). These findings suggest that geometric measures provide differential information about the cellular microstructure relative to traditional DTI measures. Results also suggest greater sensitivity for non-linear registration pipelines that maximize the anatomical information available in T1-weighted images. Clinically, rmTBI resulted in a pattern of decreased FA and increased ODI, largely overlapping in space, in conjunction with increased intracellular and free water fractions, highlighting the potential role of edema following repeated head trauma. In summary, current results suggest that geometric models of diffusion can provide relatively unique information regarding potential mechanisms of pathology that contribute to long-term neurological damage.


Asunto(s)
Traumatismos en Atletas/diagnóstico por imagen , Lesiones Encefálicas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Imagen de Difusión Tensora/métodos , Artes Marciales/lesiones , Adulto , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Lesiones Encefálicas/etiología , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Masculino , Pruebas Neuropsicológicas , Estudios Prospectivos , Análisis de Regresión , Estudios Retrospectivos , Autoinforme , Sustancia Blanca/diagnóstico por imagen
19.
J Psychiatry Neurosci ; 41(5): 312-21, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26883319

RESUMEN

BACKGROUND: Previous studies of response inhibition in patients with schizophrenia have focused on reactive inhibition tasks (e.g., stop-signal, go/no-go), primarily observing lateral prefrontal cortex abnormalities. However, recent studies suggest that purposeful and sustained (i.e., proactive) inhibition may also be affected in these patients. METHODS: Patients with chronic schizophrenia and healthy controls underwent fMRI while inhibiting motor responses during multisensory (audiovisual) stimulation. Resting state data were also collected. RESULTS: We included 37 patients with schizophrenia and 37 healthy controls in our study. Both controls and patients with schizophrenia successfully inhibited the majority of overt motor responses. Functional results indicated basic inhibitory failure in the lateral premotor and sensorimotor cortex, with opposing patterns of positive (schizophrenia) versus negative (control) activation. Abnormal activity was associated with independently assessed signs of psychomotor retardation. Patients with schizophrenia also exhibited unique activation of the pre-supplementary motor area (pre-SMA)/SMA and precuneus relative to baseline as well as a failure to deactivate anterior nodes of the default mode network. Independent resting-state connectivity analysis indicated reduced connectivity between anterior (task results) and posterior regions of the sensorimotor cortex for patients as well as abnormal connectivity between other regions (cerebellum, thalamus, posterior cingulate gyrus and visual cortex). LIMITATIONS: Aside from rates of false-positive responses, true proactive response inhibition tasks do not provide behavioural metrics that can be independently used to quantify task performance. CONCLUSION: Our results suggest that basic cortico-cortico and intracortical connections between the sensorimotor cortex and adjoining regions are impaired in patients with schizophrenia and that these impaired connections contribute to inhibitory failures (i.e., a positive rather than negative hemodynamic response).


Asunto(s)
Percepción Auditiva/fisiología , Actividad Motora/fisiología , Inhibición Proactiva , Esquizofrenia/fisiopatología , Corteza Sensoriomotora/fisiopatología , Percepción Visual/fisiología , Adulto , Mapeo Encefálico , Enfermedad Crónica , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Descanso , Esquizofrenia/diagnóstico por imagen , Psicología del Esquizofrénico , Corteza Sensoriomotora/diagnóstico por imagen
20.
Hum Brain Mapp ; 37(2): 745-55, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26598791

RESUMEN

Functional magnetic resonance imaging (fMRI) of the blood oxygen level dependent (BOLD) response has commonly been used to investigate the neuropathology underlying cognitive and sensory deficits in patients with schizophrenia (SP) by examining the positive phase of the BOLD response, assuming a fixed shape for the hemodynamic response function (HRF). However, the individual phases (positive and post-stimulus undershoot (PSU)) of the HRF may be differentially affected by a variety of underlying pathologies. The current experiment used a multisensory detection task with a rapid event-related fMRI paradigm to investigate both the positive and PSU phases of the HRF in SP and healthy controls (HC). Behavioral results indicated no significant group differences during task performance. Analyses that examined the shape of the HRF indicated two distinct group differences. First, SP exhibited a reduced and/or prolonged PSU following normal task-related positive BOLD activation in secondary auditory and visual sensory areas relative to HC. Second, SP did not show task-induced deactivation in the anterior node of the default-mode network (aDMN) relative to HC. In contrast, when performing traditional analyses that focus on the positive phase, there were no group differences. Interestingly, the magnitude of the PSU in secondary auditory and visual areas was positively associated with the magnitude of task-induced deactivation within the aDMN, suggesting a possible common neural mechanism underlying both of these abnormalities (failure in neural inhibition). Results are consistent with recent views that separate neural processes underlie the two phases of the HRF and that they are differentially affected in SP. Hum Brain Mapp 37:745-755, 2016. © 2015 Wiley Periodicals, Inc.


Asunto(s)
Percepción Auditiva/fisiología , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Esquizofrenia/fisiopatología , Percepción Visual/fisiología , Adulto , Mapeo Encefálico , Estudios de Cohortes , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Oxígeno/sangre , Psicología del Esquizofrénico
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