Frontal Volume Research Articles

Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection

BackgroundLife expectancy of successfully treated human immunodeficiency virus (HIV)–infected individuals is approaching normal longevity. The growing HIV population ≥50 years of age is now at risk of developing HIV-associated neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV), and engaging in hazardous drinking or drug consumption that can adversely affect trajectories of the healthy aging of brain structures. MethodsThis cross-sectional/longitudinal study quantified regional brain volumes from 1101 magnetic resonance imaging scans collected over 14 years in 549 participants (25 to 75 years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV-infected individuals with alcohol dependence, 222 alcohol-dependent individuals, and 199 control subjects. We tested 1) whether localized brain regions in HIV-infected individuals exhibited accelerated aging, or alternatively, nonaccelerated premature aging deficits; and 2) the extent to which alcohol or substance dependence or HCV coinfection altered brain aging trajectories. ResultsThe HIV-infected cohort exhibited steeper declining volume trajectories than control subjects, consistently in the frontal cortex. Nonaccelerated volume deficits occurred in the temporal, parietal, insular, and cingulate regions of all three diagnostic groups. Alcohol and drug dependence comorbidities and HCV coinfection exacerbated HIV-related volume deficits. Accelerated age interactions in frontal and posterior parietal volumes endured in HIV-infected individuals free of alcohol or substance dependence and HCV infection comorbidities. Functionally, poorer HIV-associated neurocognitive disorder scores and Veterans Aging Cohort Study indices correlated with smaller regional brain volumes in the HIV-infected individuals without alcohol dependence and alcohol-dependent groups. ConclusionsHIV infection itself may confer a heightened risk of accelerated brain aging, potentially exacerbated by HCV coinfection and substance dependency. Confirmation would require a prospective study with a preinfection baseline.

Increase of frontal cerebral blood volume during transcranial magnetic stimulation in depression is related to treatment effectiveness: A pilot study with near-infrared spectroscopy.

Alterations of cerebral blood flow have been reported in studies of depression treated by transcranial magnetic stimulation (TMS). However, the relation between these changes in activity during stimulation and the effectiveness of TMS is not known. The aim of this study was to determine whether changes in frontal cerebral blood volume measured as frontal hemoglobin concentration (fHbC) during TMS are correlated with clinical outcomes of treatment. Fifteen drug-resistant patients with depression underwent a standard treatment regimen of TMS to the left dorsolateral prefrontal cortex. We recorded fHbC during stimulation at the start and end of the TMS treatment series using near-infrared spectroscopy. Symptom severity was determined using the Montgomery-Åsberg Depression Rating Scale. At the start of the TMS series, fHbC increased during stimulation in a majority of patients with no relation to symptom severity. However, at the end of the series, fHbC increase during stimulation was negatively correlated with the Montgomery-Åsberg Depression Rating Scale score and positively with the score reduction. Patients showing a decreasing response of fHbC during TMS at the end of the series experienced less clinical improvement. These results suggest that the maintenance of frontal activation during stimulation in the course of TMS series is related to the effectiveness in the treatment of depression. Measurement of fHbC during stimulation is informative in the clinical use of TMS.

Accelerated executive functions decline and gray matter structural changes in middle‐aged type 1 diabetes mellitus patients with proliferative retinopathy

The aim of the present study was to determine trajectories of cognitive and cortical changes over time in middle-aged patients with type 1 diabetes mellitus (T1DM) and proliferative retinopathy. Twenty-five patients and 25 controls underwent neuropsychological assessment and neuroimaging twice in a mean (±SD) of 3.56 ± 0.65 and 3.94 ± 0.91 years, respectively (P = 0.098). Cognitive assessment included the domains of general cognitive ability, memory, information processing speed, executive functions, attention, and motor and psychomotor speed. Symmetrized percentage change in local cortical thickness, surface area, and volume was determined using the FreeSurfer 6 vertex-wise general linear model method. Analyses were performed uncorrected and corrected for baseline systolic blood pressure and depressive symptoms. In patients versus controls, accelerated executive function decline was accompanied by, but not related to, lower left frontal and temporal surface area, left parietal and right frontal thickness, and bilateral frontal and right posterior cingulate volume (family-wise error [FWE]-corrected P < 0.05 for all). In patients, lower executive performance was related to loss of right precuneus surface area (PFWE = 0.005). Higher HbA1c during follow-up was related to executive function decline (r = -0.509, P = 0.016) and loss of left hemisphere surface area (rcorrected analysis = -0.555, P = 0.007). After 3.5 years of follow-up, middle-aged T1DM patients with proliferative retinopathy, mild focal changes in executive functions, and cortical structure were found, which may indicate accelerated aging.

Pediatric Brain Development in Down Syndrome: A Field in Its Infancy.

As surprisingly little is known about the developing brain studied in vivo in youth with Down syndrome (DS), the current review summarizes the small DS pediatric structural neuroimaging literature and begins to contextualize existing research within a developmental framework. A systematic review of the literature was completed, effect sizes from published studies were reviewed, and results are presented with respect to the DS cognitive behavioral phenotype and typical brain development. The majority of DS structural neuroimaging studies describe gross differences in brain morphometry and do not use advanced neuroimaging methods to provide nuanced descriptions of the brain. There is evidence for smaller total brain volume (TBV), total gray matter (GM) and white matter, cortical lobar, hippocampal, and cerebellar volumes. When reductions in TBV are accounted for, specific reductions are noted in subregions of the frontal lobe, temporal lobe, cerebellum, and hippocampus. A review of cortical lobar effect sizes reveals mostly large effect sizes from early childhood through adolescence. However, deviance is smaller in adolescence. Despite these smaller effects, frontal GM continues to be largely deviant in adolescence. An examination of age-frontal GM relations using effect sizes from published studies and data from Lee et al. (2016) reveals that while there is a strong inverse relationship between age and frontal GM volume in controls across childhood and adolescence, this is not observed in DS. Further developmentally focused research, ideally using longitudinal neuroimaging, is needed to elucidate the nature of the DS neuroanatomic phenotype during childhood and adolescence. (JINS, 2018, 24, 966-976).

Reduced gray matter volume is correlated with frontal cognitive and behavioral impairments in Parkinson's disease

ObjectiveTo identify the brain-volume reductions associated with frontal cognitive and behavioral impairments in Parkinson's disease (PD). MethodsForty PD patients without dementia or amnesia (Hoehn and Yahr stage 3) and 10 age-matched controls underwent brain magnetic resonance imaging. Cognitive and behavioral impairments were assessed by using the Frontal Assessment Battery (FAB) and Frontal Systems Behavioral Scale (FrSBe), respectively. We applied voxel-based morphometry to investigate the correlations of regional gray matter volume with FAB, FrSBe, and physical disability. ResultsFAB was significantly lower in PD than in controls. FrSBe was significantly higher after PD onset than before, notably in the apathy subscale. FAB and FrSBe were significantly intercorrelated. In PD patients, left inferior frontal volume was positively correlated with FAB, whereas right precentral volume was negatively correlated with FrSBe total score. The brain volumes in both of these regions were not correlated with the Unified PD Rating Scale III. ConclusionBehavioral impairments in PD tended to coexist with progression of frontal cognitive impairment. Regional atrophy within the frontal lobe was associated with both frontal cognitive and behavioral impairments. However, the specific region responsible for behavioral impairment differed from that for frontal cognitive impairment. These associations were independent of physical disability.

Reduced regional volumes associated with total psychopathy scores in an adult population with childhood lead exposure

Childhood lead exposure has been correlated to acts of delinquency and criminal behavior; however, little research has been conducted to examine its potential long term influence on behavioral factors such as personality, specifically psychopathic personality. Neuroimaging studies have demonstrated that the effects of childhood lead exposure persist into adulthood, with structural abnormalities found in gray and white matter regions involved in behavioral decision making. The current study examined whether measurements of adult psychopathy were associated with neuroanatomical differences in structural brain volumes for a longitudinal cohort with measured childhood lead exposure. We hypothesized that increased total psychopathy scores and increased blood lead concentration at 78 months of age (PbB78) would be inversely associated with volumetric measures of gray and white matter brain structures responsible for executive and emotional processing. Analyses did not display a direct effect between total psychopathy score and gray matter volume; however, reduced white matter volume in the cerebellum and brain stem in relation to increased total psychopathy scores was observed. An interaction between sex and total psychopathy score was also detected. Females displayed increased gray matter volume in the frontal, temporal, and parietal lobes associated with increased total psychopathy score, but did not display any white matter volume differences. Males primarily displayed reductions in frontal gray and white matter brain volume in relation to increased total psychopathy scores. Additionally, reduced gray and white matter volume was associated with increased blood lead levels in the frontal lobes; reduced white matter volume was also observed in the parietal and temporal lobes. Females demonstrated gray and white matter volume loss associated with increased PbB78 values in the right temporal lobe, as well as reduced gray matter volume in the frontal lobe. Males displayed reduced white matter volumes associated with increased PbB78 values in the frontal, temporal, and parietal lobes. Comparison of the two primary models revealed a volumetric decrease in the white matter of the left prefrontal cortex associated with increased total psychopathy scores and increased blood lead concentration in males. The results of this study suggested that increased psychopathy scores in this cohort may be attributable to the neuroanatomical abnormalities observed and that childhood lead exposure may be influential to these outcomes.

F73. COGNITIVE CLUSTERING IN SCHIZOPHRENIA PATIENTS, THEIR FIRST-DEGREE RELATIVES AND HEALTHY SUBJECTS IS ASSOCIATED WITH ANTERIOR CINGULATE CORTEX VOLUME

BackgroundCognitive impairments are a core feature in schizophrenia patients and are also observed in first-degree relatives of the schizophrenia patients. However, substantial variability in the impairments exists within and among schizophrenia patients, first-degree relatives and healthy controls. A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories.MethodsHere, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among 81 schizophrenia patients, 20 unaffected first-degree relatives and 25 healthy controls. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (schizophrenia patients, first-degree relatives and healthy controls), cognitive clustering was performed using a k-means clustering analysis approach, and differences in the BACS subscales (verbal memory, digit sequencing, token motor, verbal fluency, symbol coding and Tower of London) among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined.ResultsAs expected, there were significant differences in the five BACS subscales among the diagnostic groups (verbal memory, F2,123=20.6, P=1.90 × 10–8; digit sequencing, F2,123=8.0, P=5.65 × 10–4; token motor, F2,123=16.0, P=6.92 × 10–7; verbal fluency, F2,123=14.8, P=1.79 × 10–6 and symbol coding, F2,123=28.8, P=5.64 × 10–11). The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal (Cluster 1, N=36), (ii) intermediate impaired (Cluster 2, N=60) and (iii) widespread impaired (Cluster 3, N=30). The cognitive subgroups were mainly affected by the clinical diagnosis (χ2=46.7, P=5.33 × 10-10), and significant differences in all BACS subscales among clusters were found (verbal memory, F2,123=64.1, P=8.49 × 10–20; digit sequencing, F2,123=35.7, P=5.89 × 10–13; token motor, F2,123=71.7, P=2.29 × 10–21; verbal fluency, F2,123=84.2, P=9.05 × 10–24; symbol coding, F2,123=115.6, P=5.70 × 10–29 and Tower of London, F2,123=6.9, P=1.43 × 10–3). The effects of the diagnosis (SCZ<FR<HC) and cognitive clusters (Clusters 3<2<1) on brain volumes overlapped in the frontal, temporal and limbic regions. Frontal and temporal volumes were mainly affected by the diagnosis, whereas the anterior cingulate cortex volumes were affected by the additive effects of diagnosis and cognition (FWE-corrected P<0.05, x, y, z=1.5, 40.5, 19.5, T=5.49).DiscussionWe investigated the cognitive heterogeneity and cognitive continuum among schizophrenia patients, first-degree relatives and healthy controls. The cognitive clustering approach without using clinical diagnoses successfully produced more homogeneous cognitive clusters: a neuropsychologically normal, an intermediately impaired and a globally impaired cognitive cluster. Clinical diagnoses (healthy controls, first-degree relatives and schizophrenia patients) were not evenly distributed into the three clusters; i.e., these clusters were mainly affected by clinical diagnoses. Both diagnoses and cognitive clusters were associated with decreased anterior cingulate cortex volumes. Our findings demonstrate a cognitive continuum among schizophrenia patients, first-degree relatives and healthy controls and support the hypothesis that cognitive impairments and the related anterior cingulate cortex volumes would be useful intermediate phenotypes in the pathophysiology of schizophrenia.

F182. SYMPTOM-RELATED STRUCTURAL BRAIN PATTERN IN PATIENTS WITH SCHIZOPHRENIA-A PARTIAL LEAST SQUARE ANALYSIS

BackgroundMultivariate neuroimaging studies of schizophrenia have revealed a generalizable neuroanatomical signature of the illness which however does not fully explain the variance of ist clinical phenotyps. A potential strategy to improve the mapping between the psychopathology and brain pathology of the disorder is to decipher the dictionary of symptom pattern and their neuroanatomical fingerprints. If successful, such a strategy could support a biologically informed revision of the taxonomy of psychosis.Methods176 patients with first episode to chronic stages of schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS) and scanned using T1-weighted magnetic resonance imaging (MRI). The patients`PANSS scores, sociodemographic data and disease course variables, as well as their grey matter volume maps (GMV) entered a multivariate Partial Least Square (PLS) analysis that decomposed unique patterns of brain-behavior covariance between these data domains into latent variales (LV). We tested the LVs for significance using nonparametric- permutation and bootstrap resampling techniques.ResultsThree LVs showed significant brain-behavioral constellations. The first pattern linked hippocampal and medial frontal cortex volume with negative symptoms, age and age of onset. The second pattern consisted of opposite correlation between positive and negative symptoms associated with positive loadings in the subcortical structures such as the thalamus, the caudate nucleus and negative loadings in the auditory, insular and medial prefrontal cortices. The third LV presented a pattern involving negative symptoms, illness duration and age of onset as well as volume reductions in the anterior insular and orbitofrotal cortices.DiscussionOur results indicate that the heterogeneity of schizophrenia can be decomposed into clinically relevant brain-behavioral phenotyps of the disorder, suggesting a biologically-informed and disease stage-sensitive stratification of schizophrenic patients. This might provide a neurobiological basis for future stratified investigations of treatment effects and prognosis both in early and advanced stages of schizophrenia.

Age sensitive associations of adolescent substance use with amygdalar, ventral striatum, and frontal volumes in young adulthood

IntroductionThis study evaluated an age sensitive model of substance use across adolescence to determine if substance use was associated with smaller volumes for an earlier developing brain region, the amygdala, a later developing region, the inferior frontal gyrus, and the ventral striatum. MethodParticipants (N = 110) were African American young adults who were members of a longitudinal cohort across childhood and adolescence. Measures of substance use were collected across early (ages 12–15 yrs.), middle (ages 16–18 yrs.), and later (ages 19–21 yrs.) adolescence; then, at age 25, a representative subset of the sample completed magnetic resonance imaging (MRI) that assessed regional brain volumes. ResultsHigher levels of substance use during early adolescence, but not middle or later adolescence, were significantly associated with smaller amygdalar volume in young adulthood. Higher levels of substance use during middle adolescence, but not early or later adolescence, were significantly associated with smaller pars opercularis volume. Substance use was not associated with the pars triangularis or ventral striatum. ConclusionThese findings support age sensitive associations between substance use and smaller gray matter volumes at age 25 and are consistent with literature supporting the differential nature of substance use and brain maturation across adolescence and into young adulthood.

The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise

The prevalence of alcohol misuse increased substantially over a decade in adults, particularly in those aged 65 years or older. Ramifications for brain structural integrity are significant, especially in older adults. To combine cross-sectional, longitudinal data to test age-alcoholism interactions and examine the association between prevalent comorbidities (drug dependence and hepatitis C virus [HCV] infection) and cortical volume deficits in alcohol dependence. During 14 years, 826 structural magnetic resonance images were acquired in 222 individuals with alcohol dependence and 199 age-matched control participants (aged 25-75 years at initial study), parcellated with a common atlas, and adjusted for brain volume. Longitudinal data were available on 116 participants with alcoholism and 96 control participants. DSM-IV criteria determined alcohol and drug diagnoses; serology testing determined HCV status. The study was conducted at SRI International and Stanford University School of Medicine from April 11, 2003, to March 3, 2017. Magnetic resonance imaging-derived regional cortical volumes corrected for supratentorial volume and sex. Of the 222 participants with alcoholism, 156 (70.3%) were men; mean (SD) age was 48.0 (10.0) years; the mean age for the 199 control participants was 47.6 (14.0) years. Participants with alcohol dependence had volume deficits in frontal (t = -5.732, P < .001), temporal (t = -3.151, P = .002), parietal (t = -5.063, P < .001), cingulate (t = -3.170, P = .002), and insular (t = -4.920, P < .001) cortices; deficits were prominent in frontal subregions and were not sex dependent. Accelerated aging occurred in frontal cortex (t = -3.019, P < .02) and precentral (t = -2.691, P < .05) and superior gyri (t = -2.763, P < .05) and could not be attributed to the amount of alcohol consumed, which was greater in younger-onset than older-onset participants with alcoholism (t = 6.1191, P < .001). Given the high drug-dependence incidence (54.5%) in the alcoholism group, analysis examined drug subgroups (cocaine, cannabis, amphetamines, opiates) compared with drug-dependence-free alcoholism and control groups. Although the alcohol plus cocaine (t = -2.310, P = .04) and alcohol plus opiate (t = -2.424, P = .04) groups had smaller frontal volumes than the drug-dependence-free alcoholism group, deficits in precentral (t = -2.575, P = .01), supplementary motor (t = -2.532, P = .01), and medial (t = -2.800, P = .01) volumes endured in drug-dependence-free participants with alcoholism compared with control participants. Those with HCV infection had greater deficits than those without HCV infection in frontal (t = 3.468, P = .01), precentral (t = 2.513, P = .03), superior (t = 2.533, P = .03), and orbital (t = 2.506, P = .03) volumes, yet total frontal (t = 2.660, P = .02), insular (t = 3.526, P = .003), parietal (t = 2.414, P = .03), temporal (t = 3.221, P = .005), and precentral (t = 3.180, P = .01) volume deficits persisted in the uninfected participants with alcoholism compared with control participants with known HCV status. Drug dependence and HCV infection compounded deleterious effects of alcohol dependence on frontal cortical volumes but could not account for the frontally distributed volume deficits in the drug-free participants with alcoholism. We speculate that age-alcohol interactions notable in frontal cortex put older adults at heightened risk for age-associated neurocompromise even if alcohol misuse is initiated later in life.

Greater body mass index is associated with reduced frontal cortical volumes among adolescents with bipolar disorder.

Higher body mass index (BMI) and obesity is common among youth with bipolar disorder (BD) and is associated with greater psychiatric illness severity, including suicidality. Obesity has been associated with frontal, temporal and subcortical volumetric reductions in adults with BD. We examined the neurostructural correlates of BMI in adolescents early in their course of BD. We processed T1-weighted images of adolescents with BD and psychiatrically healthy controls using FreeSurfer to derive a priori region of interest (ROI) volumes/cortical thickness for the frontal lobe (FL), prefrontal cortex (PFC) and orbitofrontal cortex (OFC) as well as volumes for the amygdala and hippocampus. General linear models assessed the association between BMI and the ROIs, controlling for age, sex and intracranial volume. We also conducted exploratory within-BD group and whole brain vertex-wise analyses. We included 40 adolescents with BD and 48 controls in our analyses. In addition to a main effect of BMI on the ROIs, there were significant diagnosis × BMI interaction effects on FL volumes. In the BD group only, BMI was negatively associated with FL, OFC and PFC cortical thickness. Whole brain analysis of BMI-volume correlations revealed 2 significant interaction clusters: 1 in the medial OFC and 1 in the caudal anterior cingulate cortex, with BD showing a stronger negative correlation. Reliance on BMI rather than a more nuanced measure of obesity may have influenced the findings. Our results suggest that elevated BMI among adolescents with BD is associated with frontal neurostructural differences that are not observed in controls. Prospective studies examining the direction of the observed associations and the effect of BMI optimization on brain structure in adolescents with BD are warranted.

Frontal and temporal cortical volume, white matter tract integrity, and hemispheric asymmetry in schizotypal personality disorder

Abnormalities in temporal and frontal cortical volume, white matter tract integrity, and hemispheric asymmetry have been implicated in schizophrenia-spectrum disorders. Schizotypal personality disorder can provide insight into vulnerability and protective factors in these disorders without the confounds associated with chronic psychosis. However, multimodal imaging and asymmetry studies in SPD are sparse. Thirty-seven individuals with SPD and 29 healthy controls (HC) received clinical interviews and 3T magnetic resonance T1-weighted and diffusion tensor imaging scans. Mixed ANOVAs were performed on gray matter volumes of the lateral temporal regions involved in auditory and language processing and dorsolateral prefrontal cortex involved in executive functioning, as well as fractional anisotropy (FA) of prominent white matter tracts that connect frontal and temporal lobes. In the temporal lobe regions, there were no group differences in volume, but SPD had reduced right>left middle temporal gyrus volume asymmetry compared to HC and lacked the right>left asymmetry in the inferior temporal gyrus volume seen in HC. In the frontal regions, there were no differences between groups on volume or asymmetry. In the white matter tracts, SPD had reduced FA in the left sagittal stratum and superior longitudinal fasciculus, and increased right>left asymmetry in sagittal stratum FA compared to HC. In the SPD group, lower left superior longitudinal fasciculus FA was associated with greater severity of disorganization symptoms. Findings suggest that abnormities in structure and asymmetry of temporal regions and frontotemporal white matter tract integrity are implicated in SPD pathology.

Age-Modulated Associations between KIBRA, Brain Volume, and Verbal Memory among Healthy Older Adults.

The resource modulation hypothesis suggests that the influence of genes on cognitive functioning increases with age. The KIBRA single nucleotide polymorphism rs17070145, associated with episodic memory and working memory, has been suggested to follow such a pattern, but few studies have tested this assertion directly. The present study investigated the relationship between KIBRA alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes in three groups of cognitively healthy adults—middle aged (ages 52–64, n = 38), young old (ages 65–72, n = 45), and older old (ages 73–92, n = 62)—who were carefully matched on potentially confounding variables including apolipoprotein ε4 status and hypertension. Consistent with our prediction, T carriers maintained verbal memory performance with increasing age while CC homozygotes declined. Voxel-based morphometric analysis of magnetic resonance images showed an advantage for T carriers in frontal white matter volume that increased with age. Focusing on the older old group, this advantage for T carriers was also evident in left lingual gyrus gray matter and several additional frontal white matter regions. Contrary to expectations, neither KIBRA nor the interaction between KIBRA and age predicted hippocampal volumes. None of the brain regions investigated showed a CC homozygote advantage. Taken together, these data suggest that KIBRA results in decreased verbal memory performance and lower brain volumes in CC homozygotes compared to T carriers, particularly among the oldest old, consistent with the resource modulation hypothesis.

Beyond cold and warm: an objective classification for maritime midlatitude fronts

This study introduces a detailed and objective classification for midlatitude maritime fronts. The classification is based on a principal component analysis (PCA) to determine the dominant patterns of variability between fronts. Here, fronts are defined as three‐dimensional frontal volumes, which are detected in the ERA‐Interim dataset for a large number of locations in the Atlantic, Pacific and Indian oceans during both winter and summer. In addition to the well‐established distinction between warm and cold fronts, the PCA exposes several new dimensions of variability: (i) front intensity, (ii) surface fluxes and (iii) along‐front transports, linked to the intensity of the associated conveyor belts. These new dimensions of variability are regionally and seasonally robust and a lagged composite analysis demonstrates that each of the new front types evolves in a dynamically characteristic way. Further, the new front types can be related to established ones like katafronts and anafronts. The new front types are finally redefined based on simple parameter thresholds to simplify their application in future studies.

The Brain Health Assessment for Detecting and Diagnosing Neurocognitive Disorders.

Brief cognitive screens lack the sensitivity to detect mild cognitive impairment (MCI) or support differential diagnoses. The objective of this study was to validate the 10-minute, tablet-based University of California, San Francisco (UCSF) Brain Health Assessment (BHA) to overcome these limitations. Cross-sectional. UCSF Memory and Aging Center. Older adults (N=347) (neurologically healthy controls (n=185), and individuals diagnosed with MCI (n=99), dementia (n=42), and as normal with concerns (n=21)). The BHA includes subtests of memory, executive function and speed, visuospatial skills, and language and an optional informant survey. Participants completed the Montreal Cognitive Assessment (MoCA) and criterion-standard neuropsychological tests. Standardized structural 3T brain magnetic resonance imaging was performed in 145 participants. At a fixed 85% specificity rate, the BHA had 100% sensitivity to dementia and 84% to MCI; the MoCA had 75% sensitivity to dementia and 25% to MCI. The BHA had 83% sensitivity to MCI likely due to AD and 88% to MCI unlikely due to AD, and the MoCA had 58% sensitivity to MCI likely AD and 24% to MCI unlikely AD. The BHA subtests demonstrated moderate to high correlations with the criterion-standard tests from their respective cognitive domains. Memory test performance correlated with medial temporal lobe volumes; executive and speed with frontal, parietal, and basal ganglia volumes; and visuospatial with right parietal volumes. The BHA had excellent combined sensitivity and specificity to detect dementia and MCI, including MCI due to diverse etiologies. The subtests provide efficient, valid measures of neurocognition that are critical in making a differential diagnosis.

Brain structure in women at risk of postpartum psychosis: an MRI study

Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth. The risk of PP is very high in women with a history of bipolar affective disorder or schizoaffective disorder. However, the neurobiological basis of PP remains poorly understood and no study has evaluated brain structure in women at risk of, or with, PP. We performed a cross-sectional study of 256 women at risk of PP and 21 healthy controls (HC) in the same postpartum period. Among women at risk, 11 who developed a recent episode of PP (PPE) (n = 2 with lifetime bipolar disorder; n = 9 psychotic disorder not otherwise specified) and 15 at risk women who did not develop an episode of PP (NPPE) (n = 10 with lifetime bipolar disorder; n = 1 with schizoaffective disorder; n = 1 with a history of PP in first-degree family member; n = 3 with previous PP). We obtained T1-weighted MRI scans at 3T and examined regional gray matter volumes with voxel-based morphometry and cortical thickness and surface area with Freesurfer. Women with PPE showed smaller anterior cingulate gyrus, superior temporal gyrus and parahippocampal gyrus compared to NPPE women. These regions also showed decreased surface area. Moreover, the NPPE group showed a larger superior and inferior frontal gyrus volume than the HC. These results should be interpreted with caution, as there were between-group differences in terms of duration of illness and interval between delivery and MRI acquisition. Nevertheless, these are the first findings to suggest that MRI can provide information on brain morphology that characterize those women at risk of PP more likely to develop an episode after childbirth.

Getting Lost Behavior in Patients with Mild Alzheimer's Disease: A Cognitive and Anatomical Model.

Getting lost behavior (GLB) in the elderly is believed to involve poor top-down modulation of visuospatial processing, by impaired executive functions. However, since healthy elderly and elderly with Alzheimer's disease (AD) experience a different pattern of cognitive decline, it remains unclear whether this hypothesis can explain GLB in dementia. We sought to identify whether poor executive functions and working memory modulate the relationship between visuospatial processing and prevalence of GLB in healthy elderly and patients with AD. Complementary to this, we explored whether brain regions critical for executive functions modulate the relationship between GLB and brain regions critical for visuospatial processing. Ninety-two participants with mild AD and 46 healthy age-matched controls underwent neuropsychological assessment and a structural MRI. GLB was assessed using a semistructured clinical interview. Path analysis was used to explore interactions between visuospatial deficits, executive dysfunction/working memory, and prevalence of GLB, in AD and controls independently. For both healthy controls and patients with mild AD, visuospatial processing deficits were associated with GLB only in the presence of poor working memory. Anatomically, GLB was associated with medial temporal atrophy in patients with mild AD, which was not strengthened by low frontal gray matter (GM) volume as predicted. Instead, medial temporal atrophy was more strongly related to GLB in patients with high frontal GM volumes. For controls, GLB was not associated with occipital, parietal, medial temporal, or frontal GM volume. Cognitively, a top-down modulation deficit may drive GLB in both healthy elderly and patients with mild AD. This modulation effect may be localized in the medial temporal lobe for patients with mild AD. Thus, anatomical substrates of GLB in mild AD may not follow the typical top-down modulation mechanisms often reported in the healthy aging population. Implications advance therapeutic practices by highlighting the need to target both working memory and visuospatial deficits simultaneously, and that anatomical substrates of GLB may be disease specific.

Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence

Adverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood. To investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes. A prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit. Early life adversity. Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years. The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively. Study findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.

Differences in Brain Architecture in Remote Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is brain trauma from an external impact with a loss of consciousness less than 30 min. Mild TBI results in several biopsychosocial impairments, with pronounced cognitive deficits thought to resolve within 3 months of injury. Previous research suggests that these impairments are due to a temporary inability to appropriately allocate neural resources in response to cognitive demands. Our study questioned this assumption and instead hypothesized that mTBI was associated with long-term neural disruptions and compromised brain structure integrity. By extension, we investigated the likelihood that functional restitution and cognitive resolution following mTBI may be due to some form of neurofunctional reorganization. To this end, we examined abnormalities in resting state functional connectivity and structure (volume, thickness, and fractional anisotropy) in two groups of mTBI-those with 1-10 years time post-injury (mTBI1-10), and those with 20-65 years time post-injury, relative to age-, sex-, and education-matched controls. We observed abnormalities in brain architecture only in the mTBI1-10 group, characterized by functional hypo-activation in the right frontal pole, smaller frontal pole volume, and lesser fractional anisotropy in the genu of the corpus callosum that extended near the right frontal pole. This frontal region is laterally specialized to regulate function specific to socio-emotional processes. Collectively, neural disruptions and structural insult in mTBI may persist up to 10 years following injury, but injury-related pathology may resolve with longer recovery time. Disruption to frontal-dependent function that supports socio-emotional processes also may interfere with cognitive functioning, as in the case of chronic mTBI.

Mind–Matter Interactions and the Frontal Lobes of the Brain: A Novel Neurobiological Model of Psi Inhibition

Despite a large literature on psi, which encompasses a range of experiences including putative telepathy (mind-mind connections), clairvoyance (perceiving distant objects or events), precognition (perceiving future events), and mind-matter interactions, there has been insufficient focus on the brain in relation to this controversial phenomenon. In contrast, our research is based on a novel neurobiological model suggesting that frontal brain systems act as a filter to inhibit psi and that the inhibitory mechanisms may relate to self-awareness. To identify frontal brain regions that may inhibit psi. We used mind-matter interactions to study psi in two participants with frontal lobe damage. The experimental task was to influence numerical output of a Random Event Generator translated into movement of an arrow on a computer screen to the right or left. Brain MRI was analyzed to determine frontal volume loss. The primary area of lesion overlap between the participants was in the left medial middle frontal region, an area related to self-awareness, and involved Brodmann areas 9, 10, and 32. Both participants showed a significant effect in moving the arrow to the right, i.e., contralateral to the side of primary lesion overlap. Effect sizes were much larger compared to normal participants. The medial frontal lobes may act as a biological filter to inhibit psi through mechanisms related to self-awareness. Neurobiological studies with a focus on the brain may open new avenues of research on psi and may significantly advance the state of this poorly understood field.