The authors conducted a comprehensive meta-analysis of MRI region-of-interest and voxel-based morphometry (VBM) studies in posttraumatic stress disorder (PTSD). Because patients have high rates of ...comorbid depression, an additional objective was to compare the findings to a meta-analysis of MRI studies in depression.
The MEDLINE database was searched for studies from 1985 through 2016. A total of 113 studies met inclusion criteria and were included in an online database. Of these, 66 were selected for the region-of-interest meta-analysis and 13 for the VBM meta-analysis. The region-of-interest meta-analysis was conducted and compared with a meta-analysis of major depressive disorder. Within the region-of-interest meta-analysis, three subanalyses were conducted that included control groups with and without trauma.
In the region-of-interest meta-analysis, patients with PTSD compared with all control subjects were found to have reduced brain volume, intracranial volume, and volumes of the hippocampus, insula, and anterior cingulate. PTSD patients compared with nontraumatized or traumatized control subjects showed similar changes. Traumatized compared with nontraumatized control subjects showed smaller volumes of the hippocampus bilaterally. For all regions, pooled effect sizes (Hedges' g) varied from -0.84 to 0.43, and number of studies from three to 41. The VBM meta-analysis revealed prominent volumetric reductions in the medial prefrontal cortex, including the anterior cingulate. Compared with region-of-interest data from patients with major depressive disorder, those with PTSD had reduced total brain volume, and both disorders were associated with reduced hippocampal volume.
The meta-analyses revealed structural brain abnormalities associated with PTSD and trauma and suggest that global brain volume reductions distinguish PTSD from major depression.
Human voices play a fundamental role in social communication, and areas of the adult “social brain” show specialization for processing voices and their emotional content (superior temporal sulcus, ...inferior prefrontal cortex, premotor cortical regions, amygdala, and insula) 1–8. However, it is unclear when this specialization develops. Functional magnetic resonance (fMRI) studies suggest that the infant temporal cortex does not differentiate speech from music or backward speech 9, 10, but a prior study with functional near-infrared spectroscopy revealed preferential activation for human voices in 7-month-olds, in a more posterior location of the temporal cortex than in adults 11. However, the brain networks involved in processing nonspeech human vocalizations in early development are still unknown. To address this issue, in the present fMRI study, 3- to 7-month-olds were presented with adult nonspeech vocalizations (emotionally neutral, emotionally positive, and emotionally negative) and nonvocal environmental sounds. Infants displayed significant differential activation in the anterior portion of the temporal cortex, similarly to adults 1. Moreover, sad vocalizations modulated the activity of brain regions involved in processing affective stimuli such as the orbitofrontal cortex 12 and insula 7, 8. These results suggest remarkably early functional specialization for processing human voice and negative emotions.
► Specialization for the human voice was found in the anterior STS in human infants ► This voice-sensitive area is right lateralized and in a similar location to adults ► Orbitofrontal cortex and insula activate when infants process sad vocal emotions
Stroke-induced aphasia is associated with adverse effects on quality of life and the ability to return to work. For patients and clinicians the possibility of relying on valid predictors of recovery ...is an important asset in the clinical management of stroke-related impairment. Age, level of education, type and severity of initial symptoms are established predictors of recovery. However, anatomical predictors are still poorly understood. In this prospective longitudinal study, we intended to assess anatomical predictors of recovery derived from diffusion tractography of the perisylvian language networks. Our study focused on the arcuate fasciculus, a language pathway composed of three segments connecting Wernicke's to Broca's region (i.e. long segment), Wernicke's to Geschwind's region (i.e. posterior segment) and Broca's to Geschwind's region (i.e. anterior segment). In our study we were particularly interested in understanding how lateralization of the arcuate fasciculus impacts on severity of symptoms and their recovery. Sixteen patients (10 males; mean age 60 ± 17 years, range 28-87 years) underwent post stroke language assessment with the Revised Western Aphasia Battery and neuroimaging scanning within a fortnight from symptoms onset. Language assessment was repeated at 6 months. Backward elimination analysis identified a subset of predictor variables (age, sex, lesion size) to be introduced to further regression analyses. A hierarchical regression was conducted with the longitudinal aphasia severity as the dependent variable. The first model included the subset of variables as previously defined. The second model additionally introduced the left and right arcuate fasciculus (separate analysis for each segment). Lesion size was identified as the only independent predictor of longitudinal aphasia severity in the left hemisphere beta = -0.630, t(-3.129), P = 0.011. For the right hemisphere, age beta = -0.678, t(-3.087), P = 0.010 and volume of the long segment of the arcuate fasciculus beta = 0.730, t(2.732), P = 0.020 were predictors of longitudinal aphasia severity. Adding the volume of the right long segment to the first-level model increased the overall predictive power of the model from 28% to 57% F(1,11) = 7.46, P = 0.02. These findings suggest that different predictors of recovery are at play in the left and right hemisphere. The right hemisphere language network seems to be important in aphasia recovery after left hemispheric stroke.
The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, ...from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight. However, in the current 'obesogenic' human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans. Here we show, using functional magnetic resonance imaging, that peptide YY3-36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.
The adoption into the UK of children who have been reared in severely deprived conditions provides an opportunity to study possible association between very early negative experiences and subsequent ...brain development. This cross‐sectional study was a pilot for a planned larger study quantifying the effects of early deprivation on later brain structure. We used magnetic resonance imaging (MRI) to measure the sizes of three key brain regions hypothesized to be sensitive to early adverse experiences. Our sample was a group of adoptee adolescents (N = 14) who had experienced severe early institutional deprivation in Romania and a group of non‐institutionalised controls (N = 11). The total grey and white matter volumes were significantly smaller in the institutionalised group compared with a group of non‐deprived, non‐adopted UK controls. After correcting for difference in brain volume, the institutionalised group had greater amygdala volumes, especially on the right, but no differences were observed in hippocampal volume or corpus callosum mid‐sagittal area. The left amygdala volume was also related to the time spent in institutions, with those experiencing longer periods of deprivation having a smaller left amygdala volume. These pilot findings highlight the need for future studies to confirm the sensitivity of the amygdala to early deprivation.
Disruption of the blood–brain barrier (BBB) and cerebral edema are the major pathogenic mechanisms leading to neurological dysfunction and death after ischemic stroke. The brain protects itself ...against infarction via activation of endogenous antioxidant defense mechanisms, and we here report the first evidence that sulforaphane-mediated preactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1) in the cerebral vasculature protects the brain against stroke. To induce ischemic stroke, Sprague-Dawley rats were subjected to 70min middle cerebral artery occlusion (MCAo) followed by 4, 24, or 72h reperfusion. Nrf2 and HO-1 protein expression was upregulated in cerebral microvessels of peri-infarct regions after 4–72h, with HO-1 preferentially associated with perivascular astrocytes rather than the cerebrovascular endothelium. In naïve rats, treatment with sulforaphane increased Nrf2 expression in cerebral microvessels after 24h. Upregulation of Nrf2 by sulforaphane treatment prior to transient MCAo (1h) was associated with increased HO-1 expression in perivascular astrocytes in peri-infarct regions and cerebral endothelium in the infarct core. BBB disruption, lesion progression, as analyzed by MRI, and neurological deficits were reduced by sulforaphane pretreatment. As sulforaphane pretreatment led to a moderate increase in peroxynitrite generation, we suggest that hormetic preconditioning underlies sulforaphane-mediated protection against stroke. In conclusion, we propose that pharmacological or dietary interventions aimed to precondition the brain via activation of the Nrf2 defense pathway in the cerebral microvasculature provide a novel therapeutic approach for preventing BBB breakdown and neurological dysfunction in stroke.
Very preterm (VPT) birth is associated with altered cortical development and long-term neurodevelopmental sequelae. We used voxel-based morphometry to investigate white (WM) and grey matter (GM) ...distribution in VPT adolescents and controls, and the association with gestational age and neonatal ultrasound findings in the VPT individuals. GM and WM volumes were additionally investigated in relation to adolescent neurodevelopmental outcome. Structural MRI data were acquired with a 1.5 Tesla machine in 218 VPT adolescents (<33 weeks, gestation) and 128 controls aged 14–15 years, and analysed using SPM2 software. VPT individuals compared to controls showed reduced GM in temporal, frontal, occipital cortices and cerebellum, including putamen, insula, cuneus, fusiform gyrus, thalamus and caudate nucleus, and increased GM predominantly in temporal and frontal lobes, including cingulate and fusiform gyri and cerebellum. WM loss was concentrated in the brainstem, internal capsule, temporal and frontal regions and the major fasciculi. WM excesses were observed in temporal, parietal and frontal regions. Investigation of the inter-relationships between brain regions and changes revealed that all selected areas where between-group increased and decreased WM and GM volumes differences were observed, were structurally associated, highlighting the influence that abnormalities in one brain area may exert over others. VPT individuals with evidence of periventricular haemorrhage and ventricular dilatation on neonatal ultrasound exhibited the greatest WM and GM alterations. VPT adolescents obtained lower scores than controls on measures of language and executive function and were more likely to show cognitive impairment compared to controls (27% versus 14%, respectively). Several areas where VPT individuals demonstrated decreased GM and WM volume were linearly associated with gestational age and mediated cognitive impairment. To summarize, our data demonstrates that VPT birth is associated with altered brain structure in adolescence. GM and WM alterations are associated with length of gestation and mediate adolescent neurodevelopmental impairment. Thus, anatomical brain changes may contribute to specific cognitive deficits associated with VPT birth and could be used in the identification of those individuals who may be at increased risk for cognitive impairment.
Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural ...and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous group of maltreated individuals has confirmed the presence of abnormalities in the basal ganglia. Based on these studies and known dopaminergic abnormalities from studies in experimental animals using social isolation, we used a task of monetary reward anticipation to examine the functional integrity of brain regions previously shown to be implicated in reward processing. Our sample included a group of adolescents (
= 12) who had experienced global deprivation early in their lives in Romania prior to adoption into UK families. In contrast to a nonadopted comparison group (
= 11), the adoptees did not recruit the striatum during reward anticipation despite comparable performance accuracy and latency. These results show, for the first time, an association between early institutional deprivation and brain reward systems in humans and highlight potential neural vulnerabilities resulting from such exposures.
Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, ...differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known.
We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls HC) while they view food images during functional Magnetic Resonance Imaging (fMRI).
In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area.
Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.