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1.
Front Aging Neurosci ; 13: 711579, 2021.
Article in English | MEDLINE | ID: mdl-34366830

ABSTRACT

Identifying biomarkers that can assess the risk of developing Alzheimer's Disease (AD) remains a significant challenge. In this study, we investigated the integrity levels of brain white matter in 34 patients with mild cognitive impairment (MCI) who later converted to AD and 53 stable MCI patients. We used diffusion tensor imaging (DTI) and automated fiber quantification to obtain the diffusion properties of 20 major white matter tracts. To identify which tracts and diffusion measures are most relevant to AD conversion, we used support vector machines (SVMs) to classify the AD conversion and non-conversion MCI patients based on the diffusion properties of each tract individually. We found that diffusivity measures from seven white matter tracts were predictive of AD conversion with axial diffusivity being the most predictive diffusion measure. Additional analyses revealed that white matter changes in the central and parahippocampal terminal regions of the right cingulate hippocampal bundle, central regions of the right inferior frontal occipital fasciculus, and posterior and anterior regions of the left inferior longitudinal fasciculus were the best predictors of conversion from MCI to AD. An SVM based on these white matter tract regions achieved an accuracy of 0.75. These findings provide additional potential biomarkers of AD risk in MCI patients.

2.
J Psychiatry Neurosci ; 45(6): 430-440, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32869961

ABSTRACT

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.


Subject(s)
Executive Function/physiology , Functional Neuroimaging/standards , Parietal Lobe/physiopathology , Prefrontal Cortex/physiopathology , Psychomotor Performance/physiology , Psychotic Disorders/physiopathology , Sensorimotor Cortex/physiopathology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Parietal Lobe/diagnostic imaging , Prefrontal Cortex/diagnostic imaging , Psychotic Disorders/diagnostic imaging , Sensorimotor Cortex/diagnostic imaging , Young Adult
3.
Brain Commun ; 2(2): fcaa084, 2020.
Article in English | MEDLINE | ID: mdl-32954333

ABSTRACT

Primary brain tumours often occur near eloquent regions, affecting language, motor and memory capacity, with awake mapping and tailored resection designed to preserve higher cognitive functioning. The effects of such tumours on subcortical structures, including the thalamus and basal ganglia, have been largely unexplored, in spite of the known importance of such structures to higher cognitive functioning. We sought to explore the effects of volume changes of subcortical structures on cognition, in 62 consecutive patients diagnosed with primary brain tumour and cavernous malformations, referred to our neurosurgical practice. We found right caudate to be highly predictive of intelligence, left pallidum of total neuropsychological function and right hippocampus of mood. Our study is the largest of its kind in exploring subcortical substrates of higher cognition in consecutive patients with brain tumours. This research supports prior literature, showing subcortical structures to be related to higher cognitive functioning, particularly measures of memory and executive functioning implicated in fronto-subcortical circuits. Furthermore, involvement of right mesial temporal structures in mood, further strengthens the central role of Papez circuit in emotional quality of cognition. Attention to subcortical integrity is likely to be important in discussing postsurgical cognitive outcome with patients and their families.

4.
Neuroimage ; 218: 116940, 2020 09.
Article in English | MEDLINE | ID: mdl-32422402

ABSTRACT

While the behavior of "being musically creative"- improvising, composing, songwriting, etc.-is undoubtedly a complex and highly variable one, recent neuroscientific investigation has offered significant insight into the neural underpinnings of many of the creative processes contributing to such behavior. A previous study from our research group (Bashwiner et al., 2016), which examined two aspects of brain structure as a function of creative musical experience, found significantly increased cortical surface area or subcortical volume in regions of the default-mode network, a motor planning network, and a "limbic" network. The present study sought to determine how these regions coordinate with one another and with other regions of the brain in a large number of participants (n â€‹= â€‹218) during a task-neutral period, i.e., during the "resting state." Deriving from the previous study's results a set of eleven regions of interest (ROIs), the present study analyzed the resting-state functional connectivity (RSFC) from each of these seed regions as a function of creative musical experience (assessed via our Musical Creativity Questionnaire). Of the eleven ROIs investigated, nine showed significant correlations with a total of 22 clusters throughout the brain, the most significant being located in bilateral cerebellum, right inferior frontal gyrus, midline thalamus (particularly the mediodorsal nucleus), and medial premotor regions. These results support prior reports (by ourselves and others) implicating regions of the default-mode, executive, and motor-planning networks in musical creativity, while additionally-and somewhat unanticipatedly-including a potentially much larger role for the salience network than has been previously reported in studies of musical creativity.


Subject(s)
Creativity , Music/psychology , Neural Pathways/physiology , Rest/physiology , Adolescent , Adult , Brain Mapping , Executive Function , Female , Humans , Limbic System/diagnostic imaging , Limbic System/physiology , Magnetic Resonance Imaging , Male , Nerve Net/diagnostic imaging , Nerve Net/physiology , Neural Pathways/diagnostic imaging , Surveys and Questionnaires , Young Adult
5.
J Head Trauma Rehabil ; 35(4): 270-278, 2020.
Article in English | MEDLINE | ID: mdl-32108710

ABSTRACT

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.


Subject(s)
Brain Concussion , Post-Concussion Syndrome , Adolescent , Brain Concussion/complications , Brain Concussion/diagnosis , Emergency Service, Hospital , Female , Humans , Male , Post-Concussion Syndrome/diagnosis , Prospective Studies , Quality of Life
6.
J Neurotrauma ; 37(13): 1504-1511, 2020 07 01.
Article in English | MEDLINE | ID: mdl-31964232

ABSTRACT

Pediatric mild traumatic brain injury (pmTBI) has received increased public scrutiny over the past decade, especially regarding children who experience persistent post-concussive symptoms (PPCS). However, several methods for defining PPCS exist in clinical and scientific literature, and even healthy children frequently exhibit non-specific, concussive-like symptoms. Inter-method agreement (six PPCS methods), observed misclassification rates, and other psychometric properties were examined in large cohorts of consecutively recruited adolescent patients with pmTBI (n = 162) 1 week and 4 months post-injury and in age/sex-matched healthy controls (HC; n = 117) at equivalent time intervals. Six published PPCS methods were stratified into Simple Change (e.g., International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10]) and Standardized Change (e.g., reliable change indices) algorithms. Among HC, test-retest reliability was fair to good across the 4-month assessment window, with evidence of bias (i.e., higher symptom ratings) during retrospective relative to other assessments. Misclassification rates among HC were higher (>30%) for Simple Change algorithms, with poor inter-rater reliability of symptom burden across HC and their parents. A 49% spread existed in terms of the proportion of pmTBI patients "diagnosed" with PPCS at 4 months, with superior inter-method agreement among standardized change algorithms. In conclusion, the self-reporting of symptom burden is only modestly reliable in typically developing adolescents over a 4-month period, with additional evidence for systematic bias in both adolescent and parental ratings. Significant variation existed for identifying pmTBI patients who had "recovered" (i.e., those who did not meet individual criteria for PPCS) from concussion across the six definitions, representing a considerable challenge for estimating the true incidence rate of PPCS in published literature. Although relatively straightforward to obtain, current findings question the utility of the most commonly used Simple Change scores for diagnosis of PPCS in clinical settings.


Subject(s)
Brain Concussion/classification , Brain Concussion/diagnosis , Neuropsychological Tests/standards , Post-Concussion Syndrome/classification , Post-Concussion Syndrome/diagnosis , Adolescent , Age Factors , Brain Concussion/psychology , Child , Female , Follow-Up Studies , Humans , Male , Observer Variation , Post-Concussion Syndrome/psychology , Retrospective Studies , Sex Factors
7.
J Cereb Blood Flow Metab ; 40(12): 2491-2504, 2020 12.
Article in English | MEDLINE | ID: mdl-31903838

ABSTRACT

Much attention has been paid to the effects of mild traumatic brain injury (mTBI) on cerebrovascular reactivity in adult populations, yet it remains understudied in pediatric injury. In this study, 30 adolescents (12-18 years old) with pediatric mTBI (pmTBI) and 35 age- and sex-matched healthy controls (HC) underwent clinical and neuroimaging assessments during sub-acute (6.9 ± 2.2 days) and early chronic (120.4 ± 11.7 days) phases of injury. Relative to controls, pmTBI reported greater initial post-concussion symptoms, headache, pain, and anxiety, resolving by four months post-injury. Patients reported increased sleep issues and exhibited deficits in processing speed and attention across both visits. In grey-white matter interface areas throughout the brain, pmTBI displayed increased maximal fit/amplitude of a time-shifted end-tidal CO2 regressor to blood oxygen-level dependent response relative to HC, as well as increased latency to maximal fit. The alterations persisted through the early chronic phase of injury, with maximal fit being associated with complaints of ongoing sleep disturbances during post hoc analyses but not cognitive measures of processing speed or attention. Collectively, these findings suggest that deficits in the speed and degree of cerebrovascular reactivity may persist longer than current conceptualizations about clinical recovery within 30 days.


Subject(s)
Brain Concussion/physiopathology , Carbon Dioxide/metabolism , Hypercapnia/blood , Neuroimaging/methods , Adolescent , Anxiety/epidemiology , Brain Concussion/complications , Brain Concussion/metabolism , Carbon Dioxide/blood , Case-Control Studies , Cerebrovascular Circulation/physiology , Child , Female , Gray Matter/blood supply , Gray Matter/diagnostic imaging , Gray Matter/metabolism , Headache/epidemiology , Humans , Hypercapnia/complications , Hypercapnia/physiopathology , Male , Pain/epidemiology , Post-Concussion Syndrome/diagnosis , Post-Concussion Syndrome/epidemiology , Prospective Studies , Sleep Wake Disorders/epidemiology , White Matter/blood supply , White Matter/diagnostic imaging , White Matter/metabolism
8.
Neuroimage ; 208: 116293, 2020 03.
Article in English | MEDLINE | ID: mdl-31785421

ABSTRACT

Creative cognition, as measured through divergent thinking (DT), offers insight into one's ability to generate novel ideas. Relatively little work has been done exploring the relationship between creative idea generation tasks and white matter integrity via fractional anisotropy (FA). Our previous work has shown that higher scores on DT tasks were related to reduced fractional anisotropy (FA) within the left hemisphere anterior thalamic radiation (Jung et al., 2010). However, Takeuchi et al., 2010, found positive correlations with FA and DT tasks in the prefrontal cortex and genu of the corpus callosum. The present study assessed subjects studying or working in science, technology, engineering and mathematics (STEM; N â€‹= â€‹178) for correlations in white matter FA, as related to a measure of DT. Healthy normal subjects aged (16-32 years, mean age â€‹= â€‹22.0 â€‹± â€‹3.8; F â€‹= â€‹89/178). Three idea generation DT measures were scored by three raters (α â€‹= â€‹0.71) using the consensual assessment technique, from which a composite creativity index (CCI) was derived. We found that CCI was inversely related to FA (all p â€‹< â€‹0.05, controlling for age, sex, and full scale intelligence, and corrected for multiple comparisons using family wise error), within the left hemisphere inferior frontal gyrus, inferior fronto-occipital fasciculus, cingulate gyrus, inferior longitudinal fasciculus, and right hemisphere uncinate fasciculus. These results are consistent with our previous findings, implicating lower FA in white matter regions linking broad cortical networks, now established in a much larger sample of normal healthy subjects.


Subject(s)
Cerebral Cortex/anatomy & histology , Cognition/physiology , Thinking/physiology , White Matter/anatomy & histology , Adolescent , Adult , Cerebral Cortex/diagnostic imaging , Cohort Studies , Creativity , Diffusion Tensor Imaging , Female , Humans , Male , White Matter/diagnostic imaging , Young Adult
9.
Neuroimage ; 209: 116487, 2020 04 01.
Article in English | MEDLINE | ID: mdl-31874258

ABSTRACT

Very few studies have investigated neuroanatomical correlates of "everyday" creative achievement in cohorts of normal subjects. In previous research, we first showed that scores on the Creative Achievement Questionnaire (CAQ) were associated with lower cortical thickness within the left lateral orbitofrontal gyrus (LOFG), and increased thickness of the right angular gyrus (AG) (Jung et al., 2010). Newer studies found the CAQ to be associated with decreased volume of the rostral anterior cingulate cortex (ACC), and that artistic and scientific creativity was associated with increased and decreased volumes within the executive control network and salience network (Shi et al., 2017). We desired to replicate and extend our previous study in a larger cohort (N â€‹= â€‹248), comprised of subjects studying and working in science, technology, engineering, and math (STEM). Subjects were young (Range â€‹= â€‹16-32; Mean age â€‹= â€‹21.8; s.d. â€‹= â€‹3.5) all of whom were administered the CAQ, from which we derived artistic and scientific creativity factors. All subjects underwent structural MRI on a 3 â€‹T scanner from which cortical thickness, area, and volume measures were obtained using FreeSurfer. Our results showed mostly cortical thinning in relation to total, scientific, and artistic creative achievement encompassing many regions involved in the cognitive control network (CCN) and default mode network (DMN).


Subject(s)
Achievement , Cerebral Cortex/anatomy & histology , Creativity , Nerve Net/anatomy & histology , Neuroimaging , Adolescent , Adult , Art , Cerebral Cortex/diagnostic imaging , Engineering , Female , Humans , Magnetic Resonance Imaging , Male , Mathematics , Nerve Net/diagnostic imaging , Science , Technology , Young Adult
10.
Neurology ; 94(3): e241-e253, 2020 01 21.
Article in English | MEDLINE | ID: mdl-31645467

ABSTRACT

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.


Subject(s)
Brain Concussion/classification , Brain Concussion/diagnostic imaging , Brain Concussion/pathology , Image Interpretation, Computer-Assisted/standards , Magnetic Resonance Imaging/standards , Adolescent , Child , Common Data Elements , Female , Humans , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male
11.
Hum Brain Mapp ; 40(18): 5370-5381, 2019 12 15.
Article in English | MEDLINE | ID: mdl-31456319

ABSTRACT

Although much attention has been generated in popular media regarding the deleterious effects of pediatric mild traumatic brain injury (pmTBI), a paucity of empirical evidence exists regarding the natural course of biological recovery. Fifty pmTBI patients (12-18 years old) were consecutively recruited from Emergency Departments and seen approximately 1 week and 4 months post-injury in this prospective cohort study. Data from 53 sex- and age-matched healthy controls (HC) were also collected. Functional magnetic resonance imaging was obtained during proactive response inhibition and at rest, in conjunction with independent measures of resting cerebral blood flow. High temporal resolution imaging enabled separate modeling of neural responses for preparation and execution of proactive response inhibition. A priori predictions of failed inhibitory responses (i.e., hyperactivation) were observed in motor circuitry (pmTBI>HC) and sensory areas sub-acutely and at 4 months post-injury. Paradoxically, pmTBI demonstrated hypoactivation (HC>pmTBI) during target processing, along with decreased activation within prefrontal cognitive control areas. Functional connectivity within motor circuitry at rest suggested that deficits were limited to engagement during the inhibitory task, whereas normal resting cerebral perfusion ruled out deficits in basal perfusion. In conclusion, current results suggest blood oxygen-level dependent deficits during inhibitory control may exceed commonly held beliefs about physiological recovery following pmTBI, potentially lasting up to 4 months post-injury.


Subject(s)
Brain Concussion/diagnostic imaging , Brain Concussion/psychology , Cerebrovascular Circulation/physiology , Proactive Inhibition , Psychomotor Performance/physiology , Adolescent , Brain Concussion/physiopathology , Child , Female , Humans , Male , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology
12.
Hum Brain Mapp ; 40(13): 3843-3859, 2019 09.
Article in English | MEDLINE | ID: mdl-31119818

ABSTRACT

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.


Subject(s)
Artifacts , Brain/physiology , Functional Neuroimaging/methods , Head Movements , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Adolescent , Adult , Brain/diagnostic imaging , Female , Functional Neuroimaging/standards , Humans , Image Processing, Computer-Assisted/standards , Magnetic Resonance Imaging/standards , Male , Pattern Recognition, Visual/physiology , Psychomotor Performance/physiology , Research Design , Young Adult
13.
Schizophr Res ; 208: 344-352, 2019 06.
Article in English | MEDLINE | ID: mdl-30711315

ABSTRACT

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.


Subject(s)
Cognition Disorders/psychology , Emotional Intelligence , Psychotic Disorders/psychology , Symptom Assessment/psychology , Adolescent , Adult , Bipolar Disorder/classification , Bipolar Disorder/diagnosis , Bipolar Disorder/psychology , Cognition Disorders/classification , Cognition Disorders/diagnosis , Cost of Illness , Diagnostic and Statistical Manual of Mental Disorders , Emotional Intelligence/classification , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Phenotype , Psychiatric Status Rating Scales , Psychotic Disorders/classification , Psychotic Disorders/diagnosis , Symptom Assessment/classification , Young Adult
14.
Schizophr Bull ; 45(3): 552-561, 2019 04 25.
Article in English | MEDLINE | ID: mdl-29939338

ABSTRACT

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.


Subject(s)
Attention/physiology , Brain/physiopathology , Connectome , Nerve Net/physiopathology , Proactive Inhibition , Psychomotor Performance/physiology , Schizophrenia/physiopathology , Sensorimotor Cortex/physiopathology , Adult , Brain/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Nerve Net/diagnostic imaging , Schizophrenia/diagnostic imaging , Sensorimotor Cortex/diagnostic imaging , Young Adult
15.
Hum Brain Mapp ; 40(3): 955-966, 2019 02 15.
Article in English | MEDLINE | ID: mdl-30407681

ABSTRACT

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.


Subject(s)
Cognition/physiology , Prefrontal Cortex/physiology , Reaction Time/physiology , Adult , Echo-Planar Imaging/methods , Female , Humans , Male
16.
Neurosci Biobehav Rev ; 94: 149-165, 2018 11.
Article in English | MEDLINE | ID: mdl-30098989

ABSTRACT

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.


Subject(s)
Brain Concussion/diagnostic imaging , Brain Concussion/metabolism , Animals , Biomarkers/metabolism , Child , Humans , Meta-Analysis as Topic
17.
Biol Psychiatry ; 84(9): 675-683, 2018 11 01.
Article in English | MEDLINE | ID: mdl-29921417

ABSTRACT

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.


Subject(s)
Cognition/physiology , Frontal Lobe/physiopathology , Schizophrenia/physiopathology , Theta Rhythm/physiology , Adult , Case-Control Studies , Cues , Electroencephalography , Female , Humans , Male , Neuropsychological Tests , Reaction Time , Young Adult
18.
Hum Brain Mapp ; 39(7): 2987-2996, 2018 07.
Article in English | MEDLINE | ID: mdl-29656437

ABSTRACT

Openness/Intellect (i.e., openness to experience) is the Big Five personality factor most consistently associated with individual differences in creativity. Recent psychometric evidence has demonstrated that this factor consists of two distinct aspects-Intellect and Openness. Whereas Intellect reflects perceived intelligence and intellectual engagement, Openness reflects engagement with fantasy, perception, and aesthetics. We investigated the extent to which Openness and Intellect are associated with variations in brain structure as measured by cortical thickness, area, and volume (N = 185). Our results demonstrated that Openness was correlated inversely with cortical thickness and volume in left middle frontal gyrus (BA 6), middle temporal gyrus (MTG, BA 21), and superior temporal gyrus (BA 41), and exclusively with cortical thickness in left inferior parietal lobule (BA 40), right inferior frontal gyrus (IFG, BA 45), and MTG (BA 37). When age and sex were statistically controlled for, the inverse correlations between Openness and cortical thickness remained statistically significant for all regions except left MTG, whereas the correlations involving cortical volume remained statistically significant only for left middle frontal gyrus. There was no statistically significant correlation between Openness and cortical area, and no statistically significant correlation between Intellect and cortical thickness, area, or volume. Our results demonstrate that individual differences in Openness are correlated with variation in brain structure-particularly as indexed by cortical thickness. Given the involvement of the above regions in processes related to memory and cognitive control, we discuss the implications of our findings for the possible contribution of personality to creative cognition.


Subject(s)
Cerebral Cortex/anatomy & histology , Creativity , Intelligence/physiology , Neuroimaging/methods , Personality/physiology , Adolescent , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Young Adult
19.
Brain Imaging Behav ; 12(2): 437-448, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28321608

ABSTRACT

The need for algorithms that capture subject-specific abnormalities (SSA) in neuroimaging data is increasingly recognized across many neuropsychiatric disorders. However, the effects of initial distributional properties (e.g., normal versus non-normally distributed data), sample size, and typical preprocessing steps (spatial normalization, blurring kernel and minimal cluster requirements) on SSA remain poorly understood. The current study evaluated the performance of several commonly used z-transform algorithms [leave-one-out (LOO); independent sample (IDS); Enhanced Z-score Microstructural Assessment of Pathology (EZ-MAP); distribution-corrected z-scores (DisCo-Z); and robust z-scores (ROB-Z)] for identifying SSA using simulated and diffusion tensor imaging data from healthy controls (N = 50). Results indicated that all methods (LOO, IDS, EZ-MAP and DisCo-Z) with the exception of the ROB-Z eliminated spurious differences that are present across artificially created groups following a standard z-transform. However, LOO and IDS consistently overestimated the true number of extrema (i.e., SSA) across all sample sizes and distributions. The EZ-MAP and DisCo-Z algorithms more accurately estimated extrema across most distributions and sample sizes, with the exception of skewed distributions. DTI results indicated that registration algorithm (linear versus non-linear) and blurring kernel size differentially affected the number of extrema in positive versus negative tails. Increasing the blurring kernel size increased the number of extrema, although this effect was much more prominent when a minimum cluster volume was applied to the data. In summary, current results highlight the need to statistically compare the frequency of SSA in control samples or to develop appropriate confidence intervals for patient data.


Subject(s)
Algorithms , Neuroimaging/methods , Adult , Biological Variation, Individual , Brain/diagnostic imaging , Computer Simulation , Female , Humans , Image Processing, Computer-Assisted/methods , Male , Monte Carlo Method
20.
Sci Rep ; 6: 20482, 2016 Feb 18.
Article in English | MEDLINE | ID: mdl-26888383

ABSTRACT

Creative behaviors are among the most complex that humans engage in, involving not only highly intricate, domain-specific knowledge and skill, but also domain-general processing styles and the affective drive to create. This study presents structural imaging data indicating that musically creative people (as indicated by self-report) have greater cortical surface area or volume in a) regions associated with domain-specific higher-cognitive motor activity and sound processing (dorsal premotor cortex, supplementary and pre-supplementary motor areas, and planum temporale), b) domain-general creative-ideation regions associated with the default mode network (dorsomedial prefrontal cortex, middle temporal gyrus, and temporal pole), and c) emotion-related regions (orbitofrontal cortex, temporal pole, and amygdala). These findings suggest that domain-specific musical expertise, default-mode cognitive processing style, and intensity of emotional experience might all coordinate to motivate and facilitate the drive to create music.


Subject(s)
Creativity , Functional Neuroimaging , Limbic System/diagnostic imaging , Limbic System/physiology , Motor Cortex/diagnostic imaging , Motor Cortex/physiology , Adolescent , Adult , Female , Humans , Male
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