We used magnetic resonance imaging and cortical matching algorithms to map gray matter density (GMD) in 176 normal individuals ranging in age from 7 to 87 years. We found a significant, nonlinear decline in GMD with age, which was most rapid between 7 and about 60 years, over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces. Age effects were inverted in the left posterior temporal region, where GMD gain continued up to age 30 and then rapidly declined. The trajectory of maturational and aging effects varied considerably over the cortex. Visual, auditory and limbic cortices, which are known to myelinate early, showed a more linear pattern of aging than the frontal and parietal neocortices, which continue myelination into adulthood. Our findings also indicate that the posterior temporal cortices, primarily in the left hemisphere, which typically support language functions, have a more protracted course of maturation than any other cortical region.

The circumplex model of affect proposes that all affective states arise from cognitive interpretations of core neural sensations that are the product of two independent neurophysiological systems. This model stands in contrast to theories of basic emotions, which posit that a discrete and independent neural system subserves every emotion. We propose that basic emotion theories no longer explain adequately the vast number of empirical observations from studies in affective neuroscience, and we suggest that a conceptual shift is needed in the empirical approaches taken to the study of emotion and affective psychopathologies. The circumplex model of affect is more consistent with many recent findings from behavioral, cognitive neuroscience, neuroimaging, and developmental studies of affect. Moreover, the model offers new theoretical and empirical approaches to studying the development of affective disorders as well as the genetic and cognitive underpinnings of affective processing within the central nervous system.The reigning experimental paradigm in affective neuroscience research posits that emotions can be divided into discrete and independent categories and that specific neural structures and pathways subserve each of these emotional categories. This theory of basic emotions has yielded significant advances in the understanding of affect and yet, in the fields of clinical psychology and psychiatry, it has left unsettled many important questions. The theory of basic emotions, for example, has not explained the near ubiquitous comorbid illnesses among mood disorders, nor has it resolved confusion over the neurophysiological underpinnings of affective disorders. Moreover, basic emotion theory is largely incompatible with recent findings in behavioral genetics and temperament research. Given these empirical and heuristic limitations of the theory of basic emotions, we propose that a shift is needed in the conceptual approaches taken to the study of emotion. We propose that clinicians and researchers move away from a strictly basic emotion model of affective states, where each emotion is thought to emerge from independent neural systems, to more dimensional models of emotions, in which all affective states are understood to arise from common, overlapping neurophysiological systems.Although poorly represented in psychiatry, dimensional models have a long history in psychology (Larsen & Diener, 1992;Russell, 2003;Schlosberg, 1952;Watson, Wiese, Vaidya, & Tellegen, 1999). One particular dimensional approach, termed the circumplex model of affect, proposes that all affective states arise from two fundamental neurophysiological systems, one related to valence (a pleasure-displeasure continuum) and the other to arousal, (Russell, 1980). Each emotion can be understood as a linear combination of these two dimensions, or as varying degrees of both valence and arousal (see Figure 1). Joy, for example, is conceptualized as an emotional state that is the product of strong activation in the neural systems associated wi...

Summary Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2+/- ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2+/ mice, but not in Atg7CKO neuronal autophagy deficient mice or Tsc2+/-:Atg7CKO double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR.

Spanning functions from the simplest reflex arc to complex cognitive processes, neural circuits have diverse functional roles. In the cerebral cortex, functional domains such as visual processing, attention, memory, and cognitive control rely on the development of distinct yet interconnected sets of anatomically distributed cortical and subcortical regions. The developmental organization of these circuits is a remarkably complex process that is influenced by genetic predispositions, environmental events, and neuroplastic responses to experiential demand that modulates connectivity and communication among neurons, within individual brain regions and circuits, and across neural pathways. Recent advances in neuroimaging and computational neurobiology, together with traditional investigational approaches such as histological studies and cellular and molecular biology, have been invaluable in improving our understanding of these developmental processes in humans in both health and illness. To contextualize the developmental origins of a wide array of neuropsychiatric illnesses, this review describes the development and maturation of neural circuits from the first synapse through critical periods of vulnerability and opportunity to the emergent capacity for cognitive and behavioral regulation, and finally the dynamic interplay across levels of circuit organization and developmental epochs.

Our data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome. JAMA. 2000;284:1939-1947.

Findings from previous magnetic resonance imaging studies of sex differences in gray matter have been inconsistent, with some showing proportionally increased gray matter in women and some showing no differences between the sexes. Regional sex differences in gray matter thickness have not yet been mapped over the entire cortical surface in a large sample of subjects spanning the age range from early childhood to old age. We applied algorithms for cortical pattern matching and techniques for measuring cortical thickness to the structural magnetic resonance images of 176 healthy individuals between the ages of 7 and 87 years. We also mapped localized differences in brain size. Maps of sex differences in cortical thickness revealed thicker cortices in women in right inferior parietal and posterior temporal regions even without correcting for total brain volume. In these regions, the cortical mantle is up to 0.45 mm thicker, on average, in women than in men. Analysis of a subset of 18 female and 18 male subjects matched for age and brain volume confirmed the significance of thicker gray matter in temporal and parietal cortices in females, independent of brain size differences. Further analyses were conducted in the adult subjects where gender differences were evaluated using height as a covariate, and similar sex differences were observed even when body size differences between the sexes were controlled. Together, these results suggest that greater cortical thickness in posterior temporal inferior parietal regions in females relative to males are independent of differences in brain or body size. Age-by-sex interactions were not significant in the temporoparietal region, suggesting that sex differences in these regions are present from at least late childhood and then are maintained throughout life. Male brains were larger than female brains in all locations, though male enlargement was most prominent in the frontal and occipital poles, bilaterally. Given the large sample and the large range of ages studied, these results help to address controversies in the study of central nervous system sexual dimorphisms.

Functional connectivity among brain regions has been investigated via an analysis of correlations between regional signal fluctuations recorded in magnetic resonance (MR) images obtained in a steady state. In comparison with studies of functional connectivity that utilize task manipulations, the analysis of correlations in steady state data is less susceptible to confounds arising when functionally unrelated brain regions respond in similar ways to changes in task. A new approach to identifying interregional correlations in steady state data makes use of two independent data sets. Regions of interest (ROIs) are defined and hypotheses regarding their connectivity are generated in one data set. The connectivity hypotheses are then evaluated in the remaining (independent) data set by analyzing low frequency temporal correlations between regions. The roles of the two data sets are then reversed and the process repeated, perhaps multiple times. This method was illustrated by application to the language system. The existence of a functional connection between Broca's area and Wernicke's area was confirmed in healthy subjects at rest. An increase in this functional connection when the language system was actively engaged (when subjects were continuously listening to narrative text) was also confirmed. In a second iteration of analyses, a correlation between Broca's area and a region in left premotor cortex was found to be significant at rest and to increase during continuous listening. These findings suggest that the proposed methodology can reveal the presence and strength of functional connections in high-level cognitive systems.

Reduced caudate nucleus volumes may be a good candidate marker for a trait abnormality in the structure of the basal ganglia in persons with TS. Smaller lenticular nucleus volumes may be an additional marker for the presence of comorbid obsessive-compulsive disorder and for the persistence of tic symptoms into adulthood. Brain regions other than the basal ganglia may have greater clinical relevance in determining the severity of tic symptoms.