Bradley S. Peterson

Mapping cortical change across the human life span

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: an integrative approach to affective neuroscience, cognitive development, and psychopathology.

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.

Detection of functional connectivity using temporal correlations in MR images

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 Brocas area and Wernickes 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 Brocas 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. Hum. Brain Mapping 15:247–262, 2002.

Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder

BACKGROUND Results of structural brain imaging studies of patients with attention-deficit hyperactivity disorder have shown subtle reductions in total brain volume and in volumes of the right frontal lobe and caudate nucleus. Although various conventional volumetric and voxel-based methods of image analysis have been used in these studies, regional brain size and grey-matter abnormalities have not yet been mapped over the entire cortical surface in patients with this disorder. We aimed to map these features in patients with attention-deficit hyperactivity disorder. METHODS We used high-resolution MRI and surface-based, computational image analytic techniques to map regional brain size and grey-matter abnormalities at the cortical surface in a group of 27 children and adolescents with attention-deficit hyperactivity disorder and 46 controls, who were group-matched by age and sex. FINDINGS Abnormal morphology was noted in the frontal cortices of patients with attention-deficit hyperactivity disorder, with reduced regional brain size localised mainly to inferior portions of dorsal prefrontal cortices bilaterally. Brain size was also reduced in anterior temporal cortices bilaterally. Prominent increases in grey matter were recorded in large portions of the posterior temporal and inferior parietal cortices bilaterally. INTERPRETATION The frontal, temporal, and parietal regions are heteromodal association cortices that constitute a distributed neural system, which subserves attention and behavioural inhibition. We have identified region-specific anatomical abnormalities in cortical components of attentional systems, which may help better account for the symptoms of attention-deficit hyperactivity disorder.

An fMRI study of stroop word-color interference: evidence for cingulate subregions subserving multiple distributed attentional systems

BACKGROUND The goal of this study was to model the functional connectivity of the neural systems that subserve attention and impulse control. Proper performance of the Stroop Word-Color Interference Task requires both attention and impulse control. METHODS Word-color interference was studied in 34 normal adult subjects using functional magnetic resonance imaging. RESULTS Interregional correlation analyses suggested that the anterior cingulate is coupled functionally with multiple regions throughout the cerebrum. A factor analysis of the significant regional activations further emphasized this functional coupling. The cingulate or related mesial frontal cortices loaded on each of the seven factors identified in the factor analysis. Other regions that loaded significantly on these factors have been described previously as belonging to anatomically connected circuits believed to subserve sensory tuning, receptive language, vigilance, working memory, response selection, motor planning, and motor response functions. These seven factors appeared to be oriented topographically within the anterior cingulate, with sensory, working memory, and vigilance functions positioned more rostrally, and response selection, motor planning, and motor response positioned progressively more caudally. CONCLUSIONS These findings support a parallel distributed processing model for word-color interference in which portions of the anterior cingulate cortex modify the strengths of multiple neural pathways used to read and name colors. Allocation of attentional resources is thought to modify pathway strengths by reducing cross-talk between information processing modules that subserve the competing demands of reading and color naming. The functional topography of these neural systems observed within the cingulate argues for the presence of multiple attentional subsystems, each contributing to improved task performance. The topography also suggests a role for the cingulate in coordinating and integrating the activity of these multiple attentional subsystems.

Normal Development of Brain Circuits

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.

Course of tic severity in Tourette syndrome : The first two decades

Objective. Prevalence studies indicate a 10-fold higher rate of Tourette syndrome (TS) among children compared with adults. The purpose of this investigation was to examine the course of tic severity during the first 2 decades of life. Method. A birth-year cohort of 42 TS patients followed at the Yale Child Study Center was recontacted an average of 7.3 years after their initial clinical evaluation. Data concerning the onset and course of tic severity until 18 years of age were available on 36 TS patients. A variety of statistical techniques were used to model aspects of the temporal patterning of tic severity. Results. Mean (SD) tic onset at 5.6 (2.3) years of age was followed by a progressive pattern of tic worsening. On average, the most severe period of tic severity occurred at 10.0 (2.4) years of age. In eight cases (22%), the frequency and forcefulness of the tics reached a severe level during the worst-ever period such that functioning in school was impossible or in serious jeopardy. In almost every case this period was followed by a steady decline in tic severity. By 18 years of age nearly half of the cohort was virtually tic-free. The onset of puberty was not associated with either the timing or severity of tics. Conclusions. A majority of TS patients displayed a consistent time course of tic severity. This consistency can be accurately modeled mathematically and may reflect normal neurobiological processes. Determination of the model parameters that describe each patients course of tic severity may be of prognostic value and assist in the identification of factors that differentially influence the course of tic severity.

Reduced basal ganglia volumes in Tourette's syndrome using three‐dimensional reconstruction techniques from magnetic resonance images

Using a 1.5-tesla GE Signa MR scanner, we imaged the brains of 14 right-handed Tourettes syndrome (TS) patients (11 men, three women), aged 18 to 49 years, who had minimal lifetime neuroleptic exposure. We also studied an equal number of normal controls individually matched for age, sex, and handedness and group-matched for socioeconomic status. We circumscribed basal ganglia on sequential axial images from spin-echo proton density-weighted acquisitions (TR 1,700, TE 20; slice thickness, 3 mm with 1.5-mm skip) and submitted the images for three-dimensional processing at a computer graphics workstation. Our hypothesis of lenticular nucleus volume reduction in TS was confirmed for the left- but not the right-sided nucleus. Post hoc analyses revealed smaller mean volumes of the caudate, lenticular, and globus pallidus nuclei compared with controls on both the right and left. Further analyses of basal ganglia asymmetry indices suggest that TS basal ganglia do not have the volumetric asymmetry (left greater than right) seen in normal controls. These findings confirm and extend prior phenomenologic, neuropathologic, and neuroradiologic studies that implicate the basal ganglia in the pathogenesis of TS.

Neural and behavioral substrates of mood and mood regulation

A review of behavioral and neurobiological data on mood and mood regulation as they pertain to an understanding of mood disorders is presented. Four approaches are considered: 1) behavioral and cognitive; 2) neurobiological; 3) computational; and 4) developmental. Within each of these four sections, we summarize the current status of the field and present our vision for the future, including particular challenges and opportunities. We conclude with a series of specific recommendations for National Institute of Mental Health priorities. Recommendations are presented for the behavioral domain, the neural domain, the domain of behavioral-neural interaction, for training, and for dissemination. It is in the domain of behavioral-neural interaction, in particular, that new research is required that brings together traditions that have developed relatively independently. Training interdisciplinary clinical scientists who meaningfully draw upon both behavioral and neuroscientific literatures and methods is critically required for the realization of these goals.

Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury.

Objectives: To evaluate the effect of prolonged infusion of 3% hypertonic saline (514 mEq/L) and sustained hypernatremia on refractory intracranial hypertension in pediatric traumatic brain injury patients. Design: A prospective study. Setting: A 24‐bed Pediatric Intensive Care Unit (Level III) at Childrens Hospital. Patients: We present ten children with increased intracranial pressure (ICP) resistant to conventional therapy (head elevation at 30°, normothermia, sedation, paralysis and analgesia, osmolar therapy with mannitol, loop diuretic, external vertricular drainage in five patients), controlled hyperventilation (PCO2, 28‐35 mm Hg), and barbiturate coma. We continuously monitored ICP, cerebral perfusion pressure (CPP), mean arterial pressure, central venous pressure, serum sodium concentrations, serum osmolarity, and serum creatinine. Interventions: A continuous infusion of 3% saline on a sliding scale was used to achieve a target serum sodium level that would maintain ICP <20 mm Hg once the conventional therapy and barbiturate coma as outlined above failed to control intracranial hypertension. Measurements and Main Results: The mean duration of treatment with 3% saline was 7.6 days (range, 4‐18 days). The mean highest serum sodium was 170.7 mEq/L (range, 157‐187 mEq/L). The mean highest serum osmolarity was 364.8 mosm/L (range, 330‐431 mosm/L). The mean highest serum creatinine was 1.31 mg/dL (range, 0.4‐5.0 mg/dL). There was a steady increase in serum sodium versus time zero that reached statistical significance at 24, 48, and 72 hrs (p < .01). There was a statistically significant decrease in ICP spike frequency at 6, 12, 24, 48, and 72 hrs (p < .01). There was a statistically significant increase in CPP versus time zero at 6, 12, 24, 48, and 72 hrs (p < .01). There was a statistically significant increase in serum osmolarity versus time zero at 12 hrs (p < .05) and at 24, 48, and 72 hrs (p < .01). Two patients developed acute renal failure and required continuous veno‐venous hemodialysis; these were concurrent with an episode of sepsis and multisystem organ dysfunction. Both recovered full renal function with no electrolyte abnormalities at the time of discharge. Conclusion: An increase in serum sodium concentration significantly decreases ICP and increases CPP. Hypertonic saline is an effective agent to increase serum sodium concentrations. Sustained hypernatremia and hyperosmolarity are safely tolerated in pediatric patients with traumatic brain injury. Controlled trials are needed before recommendation of widespread use.