Frontal Volume Research Articles

Metopism in adult South Africans and its relationship to frontal sinus size.

This study documents the incidences of complete and partial metopism and their possible relationship to frontal sinus volume (FSV) in a sample of modern adult black South Africans with a view to evaluating the hypothesis that metopism affects frontal sinus hypoplasia. FSV was measured from CT scans and the incidence of metopism was recorded from direct observations of dried cadaveric crania. The sex of each individual was known. Four linear cranial dimensions were used to compute a geometric mean by which to scale FSV. The incidence of partial metopism (38%) is comparable to that reported for other population samples, although there is considerable variation among these global sample frequencies. It is significantly more common in male than female South Africans. FSV in individuals with complete metopism is smaller than average but not inordinately so. On the other hand, FSV is significantly larger in individuals with partial metopism than in those that do not present with this sutural remnant. The data on FSV in individuals with and without partial metopism contradict the hypothesis that there is a relationship between partial metopism and frontal sinus hypoplasia. As such, the metopic remnant evinced by the Late Pleistocene cranium from Hofmeyr, South Africa is unlikely to be related to its very small FSV.

Complement component 4A protein levels are negatively related to frontal volumes in patients with schizophrenia spectrum disorders.

Excessive C4A-gene expression may result in increased microglia-mediated synaptic pruning. As C4A overexpression is observed in schizophrenia spectrum disorders (SSD), this mechanism may account for the altered brain morphology (i.e. reduced volume and cortical thickness) and cognitive symptoms that characterize SSD. Therefore, this study investigates the association of C4A serum protein levels with brain morphology and cognition, and in particular whether this association differs between recent-onset SSD (n=69) and HC (n=40). Serum C4A protein levels were compared between groups. Main outcomes included total gray matter volume, mean cortical thickness and cognitive performance. Regression analysis on these outcomes included C4A level, group (SSD vs. HC), and C4A*Group interactions. All statistical tests were corrected for age, sex, BMI, and antipsychotic medication dose. Follow-up analyses were performed on separate brain regions and scores on cognitive sub-tasks. The group difference in C4A levels was not statistically significant (p=0.86). The main outcomes did not show a significant interaction effect (p>0.13) or a C4A main effect (p>0.27). Follow-up analyses revealed significant interaction effects for the left medial orbitofrontal and left frontal pole volumes (p<0.001): C4A was negatively related to these volumes in SSD, but positively in HC. This study demonstrated that C4A was negatively related to - specifically - frontal brain volumes in SSD, but this relation was inverse for HC. The results support the hypothesis of complement-mediated brain volume reduction in SSD. The results also suggest that C4A has a differential association with brain morphology in SSD compared to HC.

53 REM Sleep Behavior Disorder in Parkinson’s Disease : Longitudinal Effects on Brain Lateralization

Objective:Laterality of motor symptom onset in Parkinson’s disease (PD) is well-known and under-appreciated. It is still unclear though if this laterality might have an influence on other symptoms. Specifically, REM sleep behavior disorder has been shown to be a factor that has a high probability to be lined to PD. In this study we analyzed the longitudinal effect of REM symptomatology on brain lateralization in PD.Participants and Methods:We used the baseline and 3-year visit data of 116 participants (67 without REM (PD-non-REM), 49 with REM (PD-REM)) aged 37-81 years from the Parkinson’s Progression Markers Initiative (PPMI) dataset. Statistical 3T MRI data (cortical thicknesses, areas, foldings of cortical Desikan atlas and volumes of subcortical regions) were obtained via FreeSurfer 7.1.1. Lateralization was computed using the formula: (left-right)/(lef +right). Mixed ANOVAs were performed on each region of interest.Results:Our findings showed an increased right asymmetry of the paracentral lobule area and of the pars orbitalis area and volume in PD-REM. There was a reduced right asymmetry of the parietal inferior volume at baseline in PD-REM, whereas REM symptomatology had a stable effect at the 3 years visit. At baseline, there was an increased left asymmetry of the thickness of the caudal anterior cingulate, pars orbitalis and pars triangularis regions in PD-REM. After 3 years, there was an increased right asymmetry in those regions. The precentral, frontal superior and transversal temporal gyri showed inverse results: an increased right asymmetry of the thickness at baseline and an increased left asymmetry after 3 years. Finally, REM symptomatology is associated with more significant increases of the left asymmetry of the frontal superior gyrus volume and of the right asymmetry of the supramarginal gyrus volume after 3 years than at baseline.Conclusions:These results provide evidence of the modulating effect of the disease progression on the relationship between REM symptoms and brain lateralization in PD.

46 Moderating Impact of Trauma on Brain Regions Underlying Social Cognition in Early Onset Psychosis

Objective:Previous research has found that trauma is a risk factor for developing early-onset psychosis (EOP), both exhibiting widespread structural abnormalities and social cognitive dysfunction (Hoy et al., 2012; Nair et al., 2020; Rotiker et al., 2018). However, few studies have investigated the association between trauma, neural architecture, and social behaviors. The current study examines whether trauma exposure moderates the association between cortical volume and thickness and social cognition in EOP.Participants and Methods:T1-weighted whole-brain magnetic resonance data were acquired on a 3T Siemens scanner for 23 adolescents with EOP aged 12-21 years (M = 16.12), and 20 age-matched controls (M = 17.22). Cortical volume and thickness were calculated using the Freesurfer software suite (v5.3; Reuter et al., 2012). Based on prior research, bilateral structures of interest included the rostral anterior cingulate cortex (rACC), insula, precuneus, and superior frontal cortex. Social measures included the WebCNP Emotion Recognition (KER40) and Emotion Differentiation Test (MED36) accuracy score (Gur et al., 2010), The Awareness of Social Inference Test Total Score (TASIT; McDonald et al., 2003), and Social Responsiveness Scale, 2nd Edition (SRS-2; Constantino &amp; Gruber, 2012). Trauma exposure was assessed using the Structured Clinical Interview Diagnostic (controls n = 5; EOP n = 9; First et al., 2015). Pearson’s correlations and independent t-tests were used to examine the relationship between cortical measurements and social cognition. Additionally, PROCESS macro (Hayes, 2018) was used to examine if trauma history statistically moderated the relationship between cortical measurements and social cognition performance.Results:Significant group differences in SRS-2 scores were observed, as EOP participants scored 24.272 points higher than controls (t = 20.724, p &lt; .001). Across both groups, there was a negative correlation between the SRS-2 score and precuneus volume (r = -.438, p = .011) and thickness (r = -.383, p = .028), TASIT total and superior frontal volume (r = -.349, p = .023), and KER40 and insular volume (r = -.437, p = .20). Further, the moderation analysis revealed that the relationships between precuneus volume and SRS-2 scores, precuneus thickness and MED36 scores, and rACC thickness and KER40 scores depended on experiencing trauma across both groups. Participants with trauma across groups had increased precuneus volume associated with higher SRS-2 scores (p = .0442). Experiencing trauma was also associated with lower precuneus cortical thickness and lower MED36 scores (p = .0172). Conversely, lack of trauma experience was associated with greater rACC thickness and higher KER40 scores (p = .0119).Conclusions:Our findings indicate that past traumatic experiences may be a moderating factor in the relationship between atypical volume and thickness of social brain regions and social cognition. Overall, the significant interactions between trauma exposure and increased volume and thickness in both EOP and control participants were associated with increased impairment on social cognition measures. These findings emphasize the importance of accounting for the impact of early life adversities on brain development and how it may be relevant to social impairments, especially in individuals experiencing psychosis.

Regional white matter hyperintensity volume predicts persistent cognitive impairment in acute lacunar infarct patients.

White matter hyperintensity (WMH) is often described in acute lacunar stroke (ALS) patients. However, the specific relationship between regional WMH volume and persistent cognitive impairment remains unclear. We enrolled patients with ALS who were hospitalized at the First Affiliated Hospital of Soochow University between January 2020 and November 2022. All patients were assessed for global cognitive function using the Montreal Cognitive Assessment (MoCA) scale at 14 ± 2 days and 6 months after the onset of ALS. Manifestations of chronic cerebral small vessel disease (CSVD) were assessed via MRI scan. The distributions of regional WMH were segmented, and their relationship with cognitive impairment was evaluated. A total of 129 patients were enrolled. Baseline frontal WMH volume (OR = 1.18, P = 0.04) was an independent risk factor for long-term cognitive impairment after ALS. Furthermore, the presence of WMH at the genu of the corpus callosum (GCC) at baseline (OR = 3.1, P = 0.033) was strongly associated with persistent cognitive decline. Multivariable logistic regression analysis showed that depression (OR = 6.252, P = 0.029), NIHSS score (OR = 1.24, P = 0.011), and albumin at admission (OR = 0.841, P = 0.032) were also important determinants of long-term cognitive impairment after ALS. Our study found that WMH, especially frontal WMH volume and the presence of WMH at the GCC at baseline, independently contributed to long-term cognitive decline in ALS patients. This study provides new evidence of the clinical relationship between regional WMH volume and cognitive impairment in ALS patients.

The Physical Properties of Arabica and Robusta Coffee Beans from Temanggung and Lampung

The development of processes and handling techniques, packing, and transportation of coffee beans all benefit from knowledge of the physical attributes of coffee beans. This research was done to describe the physical characteristics of green and roasted Temanggung and Lampung coffee beans. The findings revealed that Robusta roasted beans from Lampung with a moisture content of 1.70% had the highest values of bean dimensions, geometric mean diameter, arithmetic mean diameter, equivalent mean diameter, frontal surface area, surface area, and volume. Arabica green beans from Lampung and Temanggung had the highest shape index and density values, whereas Arabica roasted beans from Lampung had the highest aspect ratio and sphericity values. Arabica green beans from Temanggung and Arabica roasted beans from Lampung had moisture contents of 6.46% and 2.69%, respectively. Meanwhile, Robusta green beans from Lampung had the greatest scores for mass and porosity. To offer somewhat full information on the design factors involved in the roasting profile of a coffee roaster, other engineering properties should be investigated in future studies.

Impacts of baseline biomarkers on cognitive trajectories in subjective cognitive decline: the CoSCo prospective cohort study

BackgroundSubjective cognitive decline (SCD) is a risk factor for Alzheimer’s disease (AD); however, the rates of cognitive decline are variable according to underlying pathologies and biomarker status. We conducted an observational study and aimed to investigate baseline characteristics and biomarkers related with cognitive declines in SCD. Our study also assessed whether SCD participants showed different cognitive and biomarker trajectories according to baseline amyloid deposition.MethodsThis study is a part of a longitudinal cohort study conducted in multi-centers in South Korea between 2018 and 2021. Individuals (≥ 60 years old) with persistent cognitive complaint despite of normal cognitive functions were eligible for the study. All participants underwent neuropsychological tests, florbetaben PET scans, plasma amyloid markers, and brain MRI scans. Annual follow-up evaluations included neuropsychological tests and assessments for clinical progressions. Regional brain volumetry and amyloid burden represented by PET-based standardized uptake value ratio (SUVR) were measured. We compared cognitive and brain atrophic changes over 24 months between amyloid positive-SCD (Aβ + SCD) and amyloid negative-SCD (Aβ-SCD) groups. Baseline factors associated with cognitive outcomes were investigated.ResultsA total of 120 participants with SCD were enrolled and 107 completed follow-up evaluations. Aβ + SCD participants (n = 20, 18.5%) were older and more frequently APOE4 carriers compared with Aβ-SCD participants (n = 87). Baseline cognitive scores were not different between the two groups, except the Seoul Verbal Learning Test (SVLT) scores showing lower scores in the Aβ + SCD group. After 24 months, plasma amyloid markers were higher, and regional volumes (entorhinal, hippocampal, and pallidum) were smaller in the Aβ + SCD participants compared with Aβ-SCD participants adjusted by age, sex, and baseline volumes. SVLT delayed recall and controlled oral word association test (COWAT) scores indicated more declines in Aβ + SCD participants. Baseline left entorhinal volumes were related to verbal memory decline, while baseline frontal volumes and global SUVR values were related to frontal functional decline.ConclusionAβ + SCD participants showed more cognitive decline and medial temporal atrophic changes during 24 months. Baseline neurodegeneration and amyloid burden were related with future cognitive trajectories in SCD.Trial registrationThis study was registered at CRIS (KCT0003397).

Contextualizing the impact of prenatal alcohol and tobacco exposure on neurodevelopment in a South African birth cohort: an analysis from the socioecological perspective.

Alcohol and tobacco are known teratogens. Historically, more severe prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) have been examined as the principal predictor of neurodevelopmental alterations, with little incorporation of lower doses or ecological contextual factors that can also impact neurodevelopment, such as socioeconomic resources (SER) or adverse childhood experiences (ACEs). Here, a novel analytical approach informed by a socio-ecological perspective was used to examine the associations between SER, PAE and/or PTE, and ACEs, and their effects on neurodevelopment. N = 313 mother-child dyads were recruited from a prospective birth cohort with maternal report of PAE and PTE, and cross-sectional structural brain neuroimaging of child acquired via 3T scanner at ages 8-11 years. In utero SER was measured by maternal education, household income, and home utility availability. The child's ACEs were measured by self-report assisted by the researcher. PAE was grouped into early exposure (<12 weeks), continued exposure (>=12 weeks), and no exposure controls. PTE was grouped into exposed and non-exposed controls. Greater access to SER during pregnancy was associated with fewer ACEs (maternal education: β = -0.293,p = 0.01; phone access: β = -0.968,p = 0.05). PTE partially mediated the association between SER and ACEs, where greater SER reduced the likelihood of PTE, which was positively associated with ACEs (β = 1.110,p = 0.01). SER was associated with alterations in superior frontal (β = -1336.036, q = 0.046), lateral orbitofrontal (β = -513.865, q = 0.046), caudal anterior cingulate volumes (β = -222.982, q = 0.046), with access to phone negatively associated with all three brain volumes. Access to water was positively associated with superior frontal volume (β=1569.527, q = 0.013). PTE was associated with smaller volumes of lateral orbitofrontal (β = -331.000, q = 0.033) and nucleus accumbens regions (β = -34.800, q = 0.033). Research on neurodevelopment following community-levels of PAE and PTE should more regularly consider the ecological context to accelerate understanding of teratogenic outcomes. Further research is needed to replicate this novel conceptual approach with varying PAE and PTE patterns, to disentangle the interplay between dose, community-level and individual-level risk factors on neurodevelopment.

Structural changes of the frontal cortex in depressed mice are associated with decreased expression of brain-derived neurotrophic factor

To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05). The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.

Structural and Functional Brain Patterns Predict Formal Thought Disorder’s Severity and Its Persistence in Recent-Onset Psychosis: Results From the PRONIA Study

BackgroundFormal thought disorder (FThD) is a core feature of psychosis, and its severity and long-term persistence relates to poor clinical outcomes. However, advances in developing early recognition and management tools for FThD are hindered by a lack of insight into the brain-level predictors of FThD states and progression at the individual level. MethodsTwo hundred thirty-three individuals with recent-onset psychosis were drawn from the multisite European Prognostic Tools for Early Psychosis Management study. Support vector machine classifiers were trained within a cross-validation framework to separate two FThD symptom-based subgroups (high vs. low FThD severity), using cross-sectional whole-brain multiband fractional amplitude of low frequency fluctuations, gray matter volume and white matter volume data. Moreover, we trained machine learning models on these neuroimaging readouts to predict the persistence of high FThD subgroup membership from baseline to 1-year follow-up. ResultsCross-sectionally, multivariate patterns of gray matter volume within the salience, dorsal attention, visual, and ventral attention networks separated the FThD severity subgroups (balanced accuracy [BAC] = 60.8%). Longitudinally, distributed activations/deactivations within all fractional amplitude of low frequency fluctuation sub-bands (BACslow-5 = 73.2%, BACslow-4 = 72.9%, BACslow-3 = 68.0%), gray matter volume patterns overlapping with the cross-sectional ones (BAC = 62.7%), and smaller frontal white matter volume (BAC = 73.1%) predicted the persistence of high FThD severity from baseline to follow-up, with a combined multimodal balanced accuracy of BAC = 77%. ConclusionsWe report the first evidence of brain structural and functional patterns predictive of FThD severity and persistence in early psychosis. These findings open up avenues for the development of neuroimaging-based diagnostic, prognostic, and treatment options for the early recognition and management of FThD and associated poor outcomes.

White matter hyperintensities in the corpus callosum are associated with beta‐amyloid, neurodegeneration and cognitive performance

AbstractBackgroundWMH in the corpus callosum (CC), as previously related to AD pathology(1) and lower cognition in AD patients(2), are suggested to play an important role in AD. The Aim of this study was to substantiate the associations between WMH location, biomarkers of AD pathophysiology, and cognitive performance in the DELCODE study.Method429 participants were included (HC: 126, SCD: 165, MCI: 87, AD: 51). WMH volumes were segmented from FLAIR images. WMH volumes were adjusted for total intracranial volume and log‐transformed. Beta‐Amyloid and total Tau (Aß42 and tTau, measured in CSF) and neurodegeneration (ND, measured by hippocampal volume) were log‐transformed and used as surrogate markers for AD pathophysiology. Cognitive performance was assessed by a global cognitive composite.Path modelling, adjusted for age, sex and education, was performed to estimate direct and indirect associations between regional WMH volumes (in the CC splenium, body, genu and the frontal lobe as possible control region), AD biomarkers and cognition.ResultsThe correlation matrix (Figure 1) showed the highest correlation of Aß42 and tTau with WMH volume the splenium CC.Greater WMH volume in the splenium CC was directly associated with lower global cognition (Figure 2a, ß = ‐0.10, p = 0.01) and indirectly through Aß42 (ß = ‐0.10, p = 0.001) and ND (Figure 2b, ß = ‐0.05, p = 0.001). The same indirect association was statistically significant regarding tTau (ß = ‐0.03, p &lt; 0.001). Model outcomes were similar for the body and genu of the CC.For frontal WMH volume, the direct association with global cognition was not statistically significant (ß = ‐0.002, p = 0.96), only through indirect associations with Aß42 (ß = ‐0.05, p = 0.003) and ND (ß = ‐0.02, p = 0.05).ConclusionWMH in the CC are associated with lower cognitive performance through direct and indirect associations with Aß42 and neurodegeneration. Similar associations were seen for frontal WMH. However, a direct association between frontal WMH volume and cognition was not noticed, when considering AD biomarkers. Our study substantiates the clinical relevance and impact of WMH in the CC, in particular the splenium, in AD. 1)Gaubert et al.,2021 2)Garnier‐Crussard et al.,2021

Longitudinal brain atrophy rates in presymptomatic genetic frontotemporal dementia

AbstractBackgroundIn light of upcoming clinical trials for genetic frontotemporal dementia (FTD), it is important to identify at what age brain atrophy rates start to accelerate and deviate from normal aging effects to find the optimal starting point for treatment. We aimed to investigate longitudinal brain atrophy rates in the presymptomatic stage of genetic FTD, using normative brain volumetry software.Method34 GRN, eight MAPT, and 14 C9orf72 presymptomatic mutation carriers underwent longitudinal volumetric T1‐weighted MRI of the brain with a one‐ to two‐year interval (mean number of scans = 3.5, SD = 1.6). Images were automatically analyzed with Quantib® ND which consisted of volume measurements (CSF and grey + white matter) of lobes (left, right, and combined), cerebellum, and hippocampus. All volumes were compared to reference centile curves based on a large population‐derived sample of non‐demented individuals (n = 4951). Mixed‐effects models were fitted to analyze atrophy rates of the different gene groups as a function of age, and were corrected for sex, head coil, and scanner software version.ResultAtrophy rates of the total brain, frontal lobe, and temporal lobe differed between gene groups (all p&lt;0.002). GRN mutation carriers declined faster than the reference centile curves for all brain areas, though relative volumes remained between 5th and 75th percentile between the ages of 45 – 70. In MAPT mutation carriers, frontal lobe volume was already at the 5th percentile at age 45, and showed further decline between the ages 50‐60. Temporal lobe volume started in the 50th percentile at age 45, but showed fastest decline over time compared to other brain structures. Frontal, temporal, parietal and cerebellar volume already started below the 5th percentile compared to the reference centile curves at age 45 for C9orf72 mutation carriers, but there was minimal decline over time until the age of 60.ConclusionWe provide evidence for longitudinal brain atrophy in the presymptomatic stage of genetic FTD. The affected brain areas and the age after which atrophy rates start to accelerate and diverge from normal aging slopes differed between gene groups. These results highlight the value of normative volumetry software for disease‐tracking and staging biomarkers in genetic FTD.

Apolipoprotein C proteins in plasma non‐high‐density lipoprotein fractions and development of Alzheimer’s disease, central arterial stiffness, and cerebral small vessel disease in older adults

AbstractBackgroundPlasma non‐high‐density lipoproteins impact development of central arterial stiffness and cerebral small vessel disease (cSVD), significantly contributing to Alzheimer’s disease (AD) and related dementias (ADRDs) through an increase in cerebral amyloid beta (Aβ) burden and acceleration of atrophy in susceptible brain regions. We sought to identify proteins in three non‐HDL plasma lipoproteins (very‐low density lipoprotein [VLDL], intermediate‐density lipoprotein [IDL], low‐density lipoprotein [LDL]) and their cross‐sectional associations with brain amyloid deposition, central arterial stiffness, neuroimaging features of cSVD (e.g., white matter hyperintensity volume), brain volumes susceptible to AD and cSVD, and incidence of dementia.MethodPlasma samples from 66 participants of the Atherosclerosis Risk in Communities (ARIC) study were fractionated to isolate VLDL, IDL, and LDL and analyzed using label‐free liquid chromatography‐mass spectrometry (LC‐MS) with Data‐Independent Acquisition. Acquired MS spectra were processed using Spectronaut™ to give protein identification and relative protein abundances were calculated using R. Linear regression models were used to examine the cross‐sectional associations between protein abundances in VLDL, IDL or LDL and brain amyloid deposition (measured by amyloid PET scan), white matter hyperintensities (WMH) volume (measured by brain MRI), central arterial stiffness (carotid‐femoral and heart‐femoral pulse wave velocity), AD‐signature region, frontal, parietal, and hippocampal brain region volumes (measured by brain MRI), and incidence of dementia. Regression models were adjusted for age, sex, race, number of APOε4 alleles, and cholesterol level (if applicable). Additionally, differential analysis (student’s t‐test) was used to compare protein abundances in non‐HDL lipoproteins between participants with elevated versus normal brain amyloid deposition.ResultWe identified 50, 78, 81 proteins in VLDL, IDL, and LDL, respectively. The most significant findings were: 1) higher levels of apolipoprotein C proteins in VLDL, IDL, and LDL were associated with lower WMH volume or less central arterial stiffness; 2) lower levels of apolipoprotein C proteins in VLDL, IDL, and LDL were associated with less incidence of dementia; 3) lower levels of apolipoprotein C proteins in VLDL, IDL, and LDL for participants with elevated amyloid deposition.ConclusionThese results suggest the possible role of apolipoprotein C proteins present in non‐HDL‐lipoproteins in the development of AD, central arterial stiffness, and cSVD.

Differential Structural Brain Changes Between Responders and Nonresponders After Physical Exercise Therapy for Chronic Nonspecific Neck Pain

Physical exercise therapy is effective for some people with chronic nonspecific neck pain but not for others. Differences in exercise-induced pain-modulatory responses are likely driven by brain changes. We investigated structural brain differences at baseline and changes after an exercise intervention. The primary aim was to investigate changes in structural brain characteristics after physical exercise therapy for people with chronic nonspecific neck pain. The secondary aims were to investigate (1) baseline differences in structural brain characteristics between responders and nonresponders to exercise therapy, and (2) differential brain changes after exercise therapy between responders and nonresponders. This was a prospective longitudinal cohort study. Twenty-four participants (18 females, mean age 39.7 y) with chronic nonspecific neck pain were included. Responders were selected as those with ≥20% improvement in Neck Disability Index. Structural magnetic resonance imaging was obtained before and after an 8-week physical exercise intervention delivered by a physiotherapist. Freesurfer cluster-wise analyses were performed and supplemented with an analysis of pain-specific brain regions of interest. Various changes in grey matter volume and thickness were found after the intervention, for example, frontal cortex volume decreased (cluster-weighted P value = 0.0002, 95% CI: 0.0000-0.0004). We found numerous differences between responders and nonresponders, most notably, after the exercise intervention bilateral insular volume decreased in responders, but increased in nonresponders (cluster-weighted P value ≤ 0.0002). The brain changes found in this study may underpin clinically observed differential effects between responders and nonresponders to exercise therapy for people with chronic neck pain. Identification of these changes is an important step toward personalized treatment approaches.

Sex Estimation From the Paranasal Sinus Volumes Using Semiautomatic Segmentation, Discriminant Analyses, and Machine Learning Algorithms.

The aims of this study were to determine whether paranasal sinus volumetric measurements differ according to sex, age group, and right-left side and to determine the rate of sexual dimorphism using discriminant function analysis and machine learning algorithms. The study included paranasal computed tomography images of 100 live individuals of known sex and age. The paranasal sinuses were marked using semiautomatic segmentation and their volumes and densities were measured. Sex determination using discriminant analyses and machine learning algorithms was performed. Males had higher mean volumes of all paranasal sinuses than females ( P < 0.05); however, there were no statistically significant differences between age groups or sides ( P > 0.05). The paranasal sinus volumes of females were more dysmorphic during sex determination. The frontal sinus volume had the highest accuracy, whereas the sphenoid sinus volume was the least dysmorphic. In this study, although there was moderate sexual dimorphism in paranasal sinus volumes, the use of machine learning methods increased the accuracy of sex estimation. We believe that sex estimation rates will be significantly higher in future studies that combine linear measurements, volumetric measurements, and machine-learning algorithms.

Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome.

Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS.

Neuroimaging Correlates of Treatment Response to Transcranial Magnetic Stimulation in Bipolar Depression: A Systematic Review.

Transcranial magnetic stimulation (TMS) has become a promising strategy for bipolar disorder (BD). This study reviews neuroimaging findings, indicating functional, structural, and metabolic brain changes associated with TMS in BD. Web of Science, Embase, Medline, and Google Scholar were searched without any restrictions for studies investigating neuroimaging biomarkers, through structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT), in association with response to TMS in patients with BD. Eleven studies were included (fMRI = 4, MRI = 1, PET = 3, SPECT = 2, and MRS = 1). Important fMRI predictors of response to repetitive TMS (rTMS) included higher connectivity of emotion regulation and executive control regions. Prominent MRI predictors included lower ventromedial prefrontal cortex connectivity and lower superior frontal and caudal middle frontal volumes. SPECT studies found hypoconnectivity of the uncus/parahippocampal cortex and right thalamus in non-responders. The post-rTMS changes using fMRI mostly showed increased connectivity among the areas neighboring the coil. Increased blood perfusion was reported post-rTMS in PET and SPECT studies. Treatment response comparison between unipolar depression and BD revealed almost equal responses. Neuroimaging evidence suggests various correlates of response to rTMS in BD, which needs to be further replicated in future studies.

The effects of physical exercise on structural, functional, and biochemical brain characteristics in individuals with chronic whiplash-associated disorder: A pilot randomized clinical trial.

Exercise for people with whiplash associated disorder (WAD) induces hypoalgesic effects in some, but hyperalgesic effects in others. We investigated the exercise-induced neurobiological effects of aerobic and strengthening exercise in individuals with chronic WAD. Sixteen participants (8 WAD, 8 pain-free [CON]) were randomised to either aerobic or strengthening exercise. MRI for brain morphometry, functional MRI for brain connectivity, and magnetic resonance spectroscopy for brain biochemistry, were used at baseline and after the 8-week intervention. There were no differences in brain changes between exercise groups in either the WAD or CON group, therefore aerobic and strengthening data were combined to optimise sample size. After the exercise intervention, the CON group demonstrated increased cortical thickness (left parahippocampus: mean difference = 0.04, 95% CI = 0.07-0.00, p = 0.032; and left lateral orbital frontal cortex: mean difference = 0.03, 95% CI = 0.00-0.06, p = 0.048). The WAD group demonstrated an increase in prefrontal cortex (right medial orbital frontal) volume (mean difference = 95.57, 95% CI = 2.30-192.84, p = 0.046). Functional changes from baseline to follow-up between the default mode network and the insula, cingulate cortex, temporal lobe, and somatosensory and motor cortices, were found in the CON group, but not in the WAD group. There were no changes post-exercise in brain biochemistry. Aerobic and strengthening exercises did not exert differential effects on brain characteristics, however differences in structural and functional changes were found between WAD and CON groups. This suggests that an altered central pain modulatory response may be responsible for differential effects of exercise in individuals with chronic WAD.

Frontal sinus hypoplasia in unoperated older patients with craniosynostosis: a pilot study.

The purpose of this study is to determine whether patients with unoperated craniosynostosis have different frontal sinus pneumatization than unaffected controls. Retrospective review was performed between 2009 and 2020 of previously unoperated patients with craniosynostosis older than 5years old at first presentation to our institution. Total frontal sinus volume (FSV) was calculated using 3D volume rendering tool in Sectra IDS7 PACS system. Age-matched normative FSV data was collected from 100 normal CT scans for the control group. The two groups were statistically compared using Fisher's exact test and T-test. Study group included nine patients, 5-39years old, median age 7years. Frontal sinus pneumatization was absent in 12% of the normal 7-year-old controls, while frontal sinus pneumatization was absent in 89% of the studied craniosynostosis patients (p < .001). Mean FSV of the study group (113 ± 340 mm3) was significantly different from that of age matched control mean FSV (2016 ± 2529 mm3) (p = .027). Frontal sinus pneumatization is suppressed in unreleased craniosynostosis and may be an intracranial space conservation phenomenon. This absent frontal sinus can have implications in future frontal region trauma and frontal osteotomies.

Effect of treatment with paliperidone palmitate versus oral antipsychotics on frontal lobe intracortical myelin volume in participants with recent-onset schizophrenia: Magnetic resonance imaging results from the DREaM study.

We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9months of treatment with paliperidone palmitate (PP) compared with 9months of treatment with oral antipsychotics (OAP) in participants with recent-onset schizophrenia or schizophreniform disorder from the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial. DREaM included 3 phases: Part I, a 2-month oral run-in; Part II, a 9-month disease progression phase (PP or OAP); and Part III, 9months of additional treatment (participants receiving PP continued PP [PP/PP] and participants receiving OAP were rerandomized to receive either PP [OAP/PP] or OAP [OAP/OAP]). In Part II, magnetic resonance imaging (MRI) and functional and symptomatic assessment was performed at baseline, day 92, and day 260. ICM volume as a fraction of the entire brain volume was quantified by subtraction of a proton density image from an inversion recovery image. Within-treatment-group changes from baseline were assessed by paired t-tests. Analysis of covariance was used to analyze ICM volume changes between treatment groups, adjusting for country. The MRI analysis sample size included 71 DREaM participants (PP, 23; OAP, 48) and 64 healthy controls. At baseline, mean adjusted ICM fraction values did not differ between groups (PP, 0.057; OAP, 0.058, p=0.79). By day 92, the adjusted ICM fraction in the OAP group had decreased significantly (change from baseline, -0.002; p=0.001), whereas the adjusted ICM fraction remained unchanged from baseline in the PP group (0.000; p=0.80). At day 260, the change from baseline in adjusted ICM fraction was -0.004 (p=0.004) in the OAP group and-0.001 (p=0.728) in the PP group. The difference between treatment groups did not reach statistical significance (p=0.147). In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs. clinicaltrials.gov identifier NCT02431702.