Joel Bruss

Normal neuroanatomical variation due to age: the major lobes and a parcellation of the temporal region.

We used high-resolution MRI to investigate gray and white matter aging in the major lobes of the cerebrum (frontal, parietal, temporal, occipital) and the major sectors of the temporal lobe (temporal pole, superior temporal gyrus, infero-temporal region, parahippocampal gyrus, amygdala, hippocampus). Subjects included 87 adults between the ages of 22 and 88 years. Regions of interest were hand-traced on contiguous 1.5mm coronal slices. For the cerebrum in general, gray matter decreased linearly with age, resulting in a decline of about 9.1-9.8% between the ages of 30 and 70 years, and a decline of 11.3-12.3% by the age of 80. In contrast, white matter volume increased until the mid-50s, after which it declined at an accelerated rate. At 70 years, white matter volume was only 5.6-6.4% less than at 30 years, but by age 80, a cubic regression model predicted that the decrease would be 21.6-25.0%. Multivariate analyses indicate that the frontal gray matter was most strongly associated with age, while occipital gray and white matter were least associated. Reduction in volume in the hippocampus was best modeled by a cubic regression model rather than a linear model. No sex differences in aging were found for any regions of interest.

Sexual dimorphism and asymmetries in the gray–white composition of the human cerebrum

Using high resolution MRI scans and automated tissue segmentation, gray and white matter (GM, WM) volumes of the frontal, temporal, parietal, and occipital lobes, cingulate gyrus, and insula were calculated. Subjects included 23 male and 23 female healthy, right-handed subjects. For all structures, male volumes were greater than female, but the gray/white (G/W) ratio was consistently higher across structures in women than men. Sexual dimorphism was greater for WM than GM: most of the G/W ratio sex differences can be attributed to variation in WM volume. The corpus callosum, although larger in men, is less sexually dimorphic than the WM as a whole. Several regions demonstrate pair-wise asymmetries in G/W ratio and WM volume. Both the cingulate gyrus and insula exhibit strong asymmetries. The left cingulate gyrus is significantly larger than the right, and the G/W ratio of the left insula is significantly greater than that of the right. Although statistically significant sex differences and asymmetries are present at this level of analysis, we argue that researchers should be wary of ascribing cognitive functional significance to these patterns at this time. This is not to say, however, that these patterns are not important for understanding the natural history of the human brain, and its evolution and development.

A morphometric analysis of auditory brain regions in congenitally deaf adults.

We investigated whether variation in auditory experience in humans during development alters the macroscopic neuroanatomy of primary or auditory association cortices. Volumetric analyses were based on MRI data from 25 congenitally deaf subjects and 25 hearing subjects, all right-handed. The groups were matched for gender and age. Gray and white matter volumes were determined for the temporal lobe, superior temporal gyrus, Heschls gyrus (HG), and the planum temporale. Deaf and hearing subjects did not differ in the total volume or the gray matter volume of HG, which suggests that auditory deafferentation does not lead to cell loss within primary auditory cortex in humans. However, deaf subjects had significantly larger gray matter–white matter ratios than hearing subjects in HG, with deaf subjects exhibiting significantly less white matter in both left and right HG. Deaf subjects also had higher gray matter–white matter ratios in the rest of the superior temporal gyrus, but this pattern was not observed for the temporal lobe as a whole. These findings suggest that auditory deprivation from birth results in less myelination and/or fewer fibers projecting to and from auditory cortices. Finally, the volumes of planum temporale and HG were significantly larger in the left hemisphere for both groups, suggesting that leftward asymmetries within “auditory” cortices do not arise from experience with auditory processing.

Introduction to the non-rigid image registration evaluation project (NIREP)

Non-rigid image registration (NIR) is an essential tool for morphologic comparisons in the presence of intra- and inter-individual anatomic variations. Many NIR methods have been developed, but are especially difficult to evaluate since point-wise inter-image correspondence is usually unknown, i.e., there is no “Gold Standard” to evaluate performance. The Non-rigid Image Registration Evaluation Project (NIREP) has been started to develop, establish, maintain, and endorse a standardized set of relevant benchmarks and metrics for performance evaluation of nonrigid image registration algorithms. This paper describes the basic framework of the project.

Correlations between regional brain volumes and memory performance in anoxia.

This study was aimed at investigating the quantitative relationship between regional brain volumes (hippocampus, amygdala, as well as cerebrum, frontal lobe, parietal lobe, temporal lobe) and performance on anterograde and retrograde memory tests in anoxic patients. We used high-resolution MRI to measure brain volumes in 13 anoxic patients. Neuropsychological testing was conducted contemporaneously with MRI. To control for age and sex, neuroanatomical volume residuals were calculated using regression equations derived from a group of 87 healthy comparison participants. We found that anoxic patients with severe amnesia had hippocampal volumes that were 36% smaller than normal, whereas patients with mild or no amnesia had normal hippocampal volumes. Regional gray matter volumes in severe amnesic anoxics were substantially smaller than expected. Performances on anterograde memory tests were significantly correlated with hippocampal and regional gray matter volume residuals. There was a significant correlation between white matter volume (but not hippocampal volume) and performance on the Visual Retention Test, a multi-dimensional test of cognitive function. There were no significant correlations between neuroanatomical measures and performance on a retrograde memory test. Our results indicate a strong quantitative relationship between performance on anterograde memory tests and hippocampal and regional gray matter volume residuals. Correlations between white matter volume residuals and performance on the VRT were found to be independent of hippocampal volume. Given the strong correlation between hippocampal volume and total gray matter volume residuals, a quantitative, normalized measure of total gray matter volume may provide a good indication of clinical outcome in anoxia. We thank Natalie Denburg, Jon Spradling, and Kathy Jones for help with participant recruitment, and Jocelyn Cole for help processing the images. Research supported by Program Project Grant NINDS NS 19632 and the Mathers Foundation.

Network measures predict neuropsychological outcome after brain injury

Significance Thought depends on the brain, and cognitive neuroscience has shown that different sets of brain regions (systems) support different cognitive abilities. We hypothesized that complex cognition might be especially supported by hub brain locations that participate in many such systems. We studied neurological patients with focal brain lesions, and found that damage to hub locations produced much greater cognitive impairment than damage to other locations. This work may improve the understanding of outcomes of brain injuries (from, e.g., stroke, resection, or trauma) and help inform prognosis and rehabilitation efforts. Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as “cortical hubs” of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six “target” hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two “control” hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury.

Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting

Objectives: To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. Methods: Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. Results: Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%–89.0%), exercising at 46.8% (44.0%–49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinsons Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p < 0.05 to p < 0.001). Increase in maximum oxygen consumption correlated with improvements on the flanker task and quality of life (p < 0.05). Conclusions: Our preliminary study suggests that aerobic walking in a community setting is safe, well tolerated, and improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD. Classification of evidence: This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition.

The Insula and Evaluative Processes

The insula has been implicated as a component of central networks subserving evaluative and affective processes. This study examined evaluative valence and arousal ratings in response to picture stimuli in patients with lesions of the insula and two contrast groups: a control-lesion group (the primary contrast group) and an amygdala-lesion group. Patients rated the positivity and negativity of picture stimuli (from very unpleasant to very pleasant) and how emotionally arousing they found the pictures to be. Compared with patients in the control-lesion group, patients with insular lesions reported reduced arousal in response to both unpleasant and pleasant stimuli, as well as marked attenuation of valence ratings. In contrast, the arousal ratings of patients with amygdala lesions were selectively attenuated for unpleasant stimuli, and these patients’ positive and negative valence ratings did not differ from those of the control-lesion group. Results support the view that the insular cortex may play a broad role in integrating affective and cognitive processes, whereas the amygdala may have a more selective role in affective arousal, especially for negative stimuli.

Damage to insula abolishes cognitive distortions during simulated gambling

Significance Gambling games are associated with a distorted psychological processing of random sequences (the gambler’s fallacy) and unrewarded outcomes that fall close to a jackpot (near misses). Problem gamblers appear more susceptible to these effects. Here, we show that these two gambling distortions are disrupted in patients with brain injury affecting the insula compared with patients with damage to the ventromedial prefrontal cortex or amygdala. In a roulette task (red/black predictions), comparison groups chose either color less after longer runs of that color outcome. On a slot machine task, comparison groups rated higher motivation following near misses relative to full misses. Our results generate a clinical hypothesis that, in disordered gambling, these cognitions may be underpinned by excessive recruitment of insula circuitry. Gambling is a naturalistic example of risky decision-making. During gambling, players typically display an array of cognitive biases that create a distorted expectancy of winning. This study investigated brain regions underpinning gambling-related cognitive distortions, contrasting patients with focal brain lesions to the ventromedial prefrontal cortex (vmPFC), insula, or amygdala (“target patients”) against healthy comparison participants and lesion comparison patients (i.e., with lesions that spare the target regions). A slot machine task was used to deliver near-miss outcomes (i.e., nonwins that fall spatially close to a jackpot), and a roulette game was used to examine the gambler’s fallacy (color decisions following outcome runs). Comparison groups displayed a heightened motivation to play following near misses (compared with full misses), and manifested a classic gambler’s fallacy effect. Both effects were also observed in patients with vmPFC and amygdala damage, but were absent in patients with insula damage. Our findings indicate that the distorted cognitive processing of near-miss outcomes and event sequences may be ordinarily supported by the recruitment of the insula. Interventions to reduce insula reactivity could show promise in the treatment of disordered gambling.

Effects of spatial transformation on regional brain volume estimates

Spatial transformation of MR brain images is a standard tool used in automated anatomical parcellation and other quantitative and qualitative methods to assess brain tissue volume, composition, and distribution. Despite widespread use, the quantitative effects of spatial transformation on regional brain volume estimates have been little studied. We report on the effects of transformation on regional brain volumes of 38 (17M, 21F) manually parcellated brains. After tracing in native space, regions of interest were transformed using a classic piecewise-linear Talairach transformation (Tal) or a nonlinear registration (AIR 5th order nonlinear algorithm, 158 parameters) to one of three Talairach-based templates: 1) Tal50, constructed from 50 Talairach-transformed normal brains, 2) the MNI 305 atlas, 3) IA38, constructed from MNI305-transformed scans of the 38 subjects used in this study. Native volumes were compared to the transformed volumes. We found that: 1) significant group-level differences can be obtained in transformed data sets that are in the opposite direction of effects obtained in native space; 2) the effects of transformation are heterogeneous across brain regions, even after covarying for total brain volume and age; 3) volumetric intra-class correlations between native and transformed brains differ by registration method and template choice, region, and tissue type; and 4) transformed brains produced hippocampus and corpus callosum volume proportions that were significantly different from those obtained in native space. Our results suggest that region-based volumetric differences uncovered by spatial-transformation-based methods should be replicated in native-space brains, and that meta-analyses should take into account whether volumes are determined using spatially-transformed images and/or specific automated methods.