Search

This study tested the hypothesis that dorsolateral prefrontal cortex deficits contribute to both working memory and long-term memory disturbances in schizophrenia. It also examined whether such deficits were more severe for verbal than nonverbal stimuli. Functional magnetic resonance imaging was used to assess cortical activation during performance of verbal and nonverbal versions of a working memory task and both encoding and recognition tasks in 38 individuals with schizophrenia and 48 healthy controls. Performance of both working memory and long-term memory tasks revealed disturbed dorsolateral prefrontal cortex activation in schizophrenia, although medial temporal deficits were also present. Some evidence was found for more severe cognitive and functional deficits with verbal than nonverbal stimuli, although these results were mixed.

Frontal contributions to cognitive decline in aging were explored using functional MRI. Frontal regions active in younger adults during self-initiated (intentional) memory encoding were under-recruited in older adults. Older adults showed less activity in anterior-ventral regions associated with controlled use of semantic information. Under-recruitment was reversed by requiring semantic elaboration suggesting it stemmed from difficulty in spontaneous recruitment of available frontal resources. In addition, older adults recruited multiple frontal regions in a nonselective manner for both verbal and nonverbal materials. Lack of selectivity was not reversed during semantically directed encoding even when under-recruitment was diminished. These findings suggest two separate forms of age-associated change in frontal cortex: under-recruitment and nonselective recruitment. The former is reversible and potentially amenable to cognitive training; the latter may reflect a less malleable change associated with cognitive decline in advanced aging.

Previous studies have suggested that recovery or compensation of language function after a lesion in the left hemisphere may depend on mechanisms in the right hemisphere. However, a direct relationship between performance and right hemisphere activity has not been established. Here, we show that patients with left frontal lesions and partially recovered aphasia learn, at a normal rate, a novel word retrieval task that requires the damaged cortex. Verbal learning is accompanied by specific response decrements in right frontal and right occipital cortex, strongly supporting the compensatory role of the right hemisphere. Furthermore, responses in left occipital cortex are abnormal and not modulated by practice. These findings indicate that frontal cortex is a source of top-down signals during learning.

Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes-no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e.g., FP-PFC in LTM retrieval).

Neuroimaging studies are increasingly performed in macaque species, including the pig-tailed macaque (Macaca nemestrina). At times experimental questions can be answered by analysis of functional images in individual subjects and reference to a structural image in that subject. However, coregistration of functional brain images across many subjects offers the experimental advantage of enabling voxel-based analysis over multiple subjects and is therefore widely used in human studies. Voxel-based coregistration methods require a high-quality 3D template image. We created such templates, derived from T1-weighted MRI and blood-flow PET images from 12 nemestrina monkeys. We designed the macaque templates to be maximally compatible with the baboon template images described in a companion paper, to facilitate cross-species comparison of functional imaging data. Here we present data showing the reliability and validity of automatic image registration to the template. Alignment of selected internal fiducial points was accurate to within 1.9 mm overall (mean) even across species. The template images, along with copies aligned to the UCLA nemestrina brain atlas, are available on the Internet (purl.org/net/kbmd/n2k) and can be used as targets with any image registration software.

Brain imaging based on functional MRI (fMRI) provides a powerful tool for characterizing age-related changes in functional anatomy. However, between-population comparisons confront potential differences in measurement properties. The present experiment explores the feasibility of conducting fMRI studies in nondemented and demented older adults by measuring hemodynamic response properties in an event-related design. A paradigm involving repeated presentation of sensory-motor response trials was administered to 41 participants (14 young adults, 14 nondemented older adults, and 13 demented older adults). For half of the trials a single sensory-motor event was presented in isolation and in the other half in pairs. Hemodynamic response characteristics to the isolated events allowed basic response properties (e.g., amplitude and variance) between subject groups to be contrasted. The paired events further allowed the summation properties of the hemodynamic response to be characterized. Robust and qualitatively similar activation maps were produced for all subject groups. Quantitative results showed that for certain regions, such as in the visual cortex, there were marked reductions in the amplitude of the hemodynamic response in older adults. In other regions, such as in the motor cortex, relatively intact response characteristics were observed. These results suggest caution should be exhibited in interpreting simple main effects in response amplitude between subject groups. However, across all regions examined, the summation of the hemodynamic response over trials was highly similar between groups. This latter finding suggests that, even if absolute measurement differences do exist between subject groups, relative activation change should be preserved. Designs that rely on group interactions between task conditions, parametric manipulations, or group interactions between regions should provide valuable data for making inferences about functional-anatomic changes between different populations.

Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO 2 ) in physiologically activated brain states remains the subject of debates. Recently it was suggested that CBF is tightly coupled to oxidative metabolism in a nonlinear fashion. As part of this hypothesis, mathematical models of oxygen delivery to the brain have been described in which disproportionately large increases in CBF are necessary to sustain even small increases in CMRO 2 during activation. We have explored the coupling of CBF and oxygen delivery by using two complementary methods. First, a more complex mathematical model was tested that differs from those recently described in that no assumptions were made regarding tissue oxygen level. Second, [ 15 O] water CBF positron emission tomography (PET) studies in nine healthy subjects were conducted during states of visual activation and hypoxia to examine the relationship of CBF and oxygen delivery. In contrast to previous reports, our model showed adequate tissue levels of oxygen could be maintained without the need for increased CBF or oxygen delivery. Similarly, the PET studies demonstrated that the regional increase in CBF during visual activation was not affected by hypoxia. These findings strongly indicate that the increase in CBF associated with physiological activation is regulated by factors other than local requirements in oxygen.

Temporal structure has a major role in human understanding of everyday events. Observers are able to segment ongoing activity into temporal parts and sub-parts that are reliable, meaningful and correlated with ecologically relevant features of the action. Here we present evidence that a network of brain regions is tuned to perceptually salient event boundaries, both during intentional event segmentation and during naive passive viewing of events. Activity within this network may provide a basis for parsing the temporally evolving environment into meaningful units.

A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

To investigate differences in water diffusion between white matter and gray matter in acute to early subacute stroke with diffusion-tensor magnetic resonance (MR) imaging.Twelve patients with unilateral middle cerebral arterial infarcts were examined with diffusion tensor-encoded echo-planar MR imaging 17 hours to 5 days after stroke onset. Isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) images were computed. (D) values were measured in ischemic and contralateral gray matter and white matter by using A(sigma) images to differentiate white matter from gray matter. (D) images were compared with unidirectional and directionally averaged diffusion-weighted images.In all patients, (D) images showed two distinct levels of diffusion reduction in the infarct; more severe reduction occurred exclusively in white matter. (D) values were significantly less in infarcted white matter than in infarcted gray matter, whereas (D) values in the contralateral white matter and gray matter were not significantly different. Relative to the contralateral side, (D) values in the infarct were reduced by 46% in white matter and by 31% in gray matter (P.001). Diffusion-weighted imaging caused underestimation of the magnitude and, in some cases, the spatial extent of the white matter diffusion abnormality.Isotropic diffusion is more reduced in white matter than in gray matter in acute to early subacute middle cerebral arterial stroke. Diffusion-tensor imaging may be more sensitive than diffusion-weighted imaging to white matter ischemia.

Regional cerebral blood flow (BF) was examined in regions of the medial prefrontal cortex (MPFC) with positron-emission tomography while subjects performed two cognitive tasks, reading nouns aloud and generating appropriate verbs for the same nouns. The control task was passive viewing of the same words. BF was reduced in regions of the MPFC during word reading and naïve verb generation, relative to a control state in which the subjects passively viewed nouns. Practicing verb generation produced improved performance, as measured by response time, which was strongly correlated with further reductions in MPFC and hypothalamic BF. After practice, when verb generation was performed on a novel list of words, reaction times slowed and the pattern of MPFC BF reverted to that seen in the word reading and naïve conditions. A separate behavioral study of the verb-generation task indicated that anxiety, high during naïve use-generation as measured by heart rate and self-report, decreased with practice on the task but returned with the introduction of a novel list of words. Taken together, these results suggest that the MPFC is part of a network, including the hypothalamus and brainstem, whose activity reflects a dynamic interplay between cognitive task performance and emotion.

Functional magnetic resonance imaging (fMRI) was used to compare directly episodic encoding and retrieval. During encoding, subjects studied visually presented words and reported via keypress whether each word represented a pleasant or unpleasant concept (intentional, deep encoding). During the retrieval phase, subjects indicated (via keypress) whether visually presented words had previously been studied. No reliable differences were found during the recognition phase for words that had been previously studied and those that had not been studied. Areas preferentially active during encoding (relative to retrieval) included left superior frontal cortex, medial frontal cortex, left superior temporal cortex, posterior cingulate, left parahippocampal gyrus, and left inferior frontal gyrus. Regions more active in retrieval than encoding included bilateral inferior parietal cortex, bilateral precuneus, right frontal polar cortex, right dorsolateral prefrontal cortex, and right inferior frontal/insular cortex.

Two experiments used functional magnetic resonance imaging (fMRI) to examine the cortical areas involved in establishing an expectation about the direction of motion of an upcoming object and applying that expectation to the analysis of the object. In Experiment 1, subjects saw a stationary cue that either indicated the direction of motion of a subsequent test stimulus (directional cue) or provided no directional information (neutral cue). Their task was to detect the presence of coherent motion in the test stimulus. The stationary directional cue produced larger modulations than the neutral cue, with respect to a passive viewing baseline, both in motion-sensitive areas such as left MT+ and the anterior intraparietal sulcus, as well as motion-insensitive areas such as the posterior intraparietal sulcus and the junction of the left medial precentral sulcus and superior frontal sulcus. Experiment 2 used an event-related fMRI technique to separate signals during the cue period, in which the expectation was encoded and maintained, from signals during the subsequent test period, in which the expectation was applied to the test object. Cue period activations from a stationary, directional cue included many of the same motion-sensitive and -insensitive areas from Experiment 1 that produced directionally specific modulations. Prefrontal activations were not observed during the cue period, even though the stationary cue information had to be translated into a format appropriate for influencing motion detection, and this format was maintained for the duration of the cue period (∼5 sec).

To obtain normative human cerebral data and evaluate the anatomic information in quantitative diffusion anisotropy magnetic resonance (MR) imaging.Quantitative diffusion anisotropy MR images were obtained in 13 healthy adults by using single-shot echo-planar MR imaging and a combination of tetrahedral and orthogonal gradient encoding (whole-brain coverage in about 1 minute). White matter (WM) anatomy was assessed at visual inspection, and values were measured in various brain regions. Different anisotropy measures, including total anisotropy (A sigma), were compared on the basis of information content, rotational invariance, and susceptibility to noise. Partial volume and noise effects were simulated.Anisotropy MR images depicted WM features not typically seen on conventional MR images (e.g., external capsule, thalamic substructures, basal ganglia, occipital WM, thickness of the internal capsule). Statistically significant anisotropy differences occurred across brain regions, which were reproducible within and across subjects. A sigma was highest in commissural WM and progressively lower in projection and association WM. This order paralleled that of known resistance to spread of vasogenic edema, which suggested that anisotropy may be sensitive to WM histologic structure. Gray matter (GM) A sigma data were consistent with zero anisotropy, and partial volume WM-GM effects were approximately linear. A sigma image quality could be effectively improved by means of averaging.Quantitative diffusion anisotropy images can be obtained rapidly and demonstrate subtle WM anatomy. Different histologic types of WM have significant and reproducible anisotropy differences.

Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109–110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.

This chapter reviews many technical as well as conceptual issues involved in the surface-based analyses of cerebral cortex. The degree of accuracy associated with different surface representations is an issue of particular importance. For some applications, it is sufficient to see results portrayed on a cortical surface that is topologically accurate (that is, has no holes or tangles), even if it contains substantial geometric inaccuracies or distortion. For other purposes such as morphometric analyses, it is desirable to know the precise extent of the cortical surface (plus its thickness) associated with specific regions that have been delimited geographically or functionally. The visualization and analysis methods discussed and illustrated in this chapter involve a variety of software packages. Some of this software has only recently been made available, and some of it is still under active development. The goal of surface reconstruction is to obtain an accurate representation of the desired cortical layer by a process that is reliable, efficient, and entails minimal user interaction. It is important not only to continue improving the accuracy of surface reconstructions but also to refine the methods for assessing uncertainties and regional biases in surface area measurements.

Previous research into development of a gallium-radiolabeled agent that crosses the blood- brain barrier has met with limited success. In this study, we focused our attention on a Ga(III) complex of a 4-coordinate amine trithiolate tripod ligand, tris(2-mercaptobenzyl) amine (S3N). The Ga(III) S3N complex is small, neutral, and lipophilic, meeting the requirements for a potential brain imaging agent. The Ga-68 complex was easily formed with a radiochemical purity of >95%. In vitro stability of the Ga-S3N complex, determined in rat serum incubated at 37°C, was greater than 95% intact a t2hb ysilica gel and reversed-phase radio-thin layer chromatography. Biodistribution studies conducted in female Sprague- Dawley rats showed the complex cleared rapidly from the blood with initial high liver uptake followed by rapid washout. Significant uptake was observed in the brain, with brain:blood ratios increasing from 0.11 at 2 min postinjection to 3.8 at 60 min postinjection. Uptake was also observed in the heart going from a heart:blood ratio of 2.3 at 2 min postinjection to 11 at 60 min postinjection. Molecular mechanics were used to determine the coordination number, and demonstrated that the Ga(III) complex prefers to be 4-coordinate. Imaging studies with 68 Ga-S3N in a Nemestrina macaque showed significant brain uptake, similar to other lipophilic agents. The extraction of 68 Ga-S3N into the brains of both rodents and primates, higher than any 68 Ga agent reported in the literature, suggests that this compound may have potential as a brain imaging agent for positron emission tomography. NUCL MED BIOL 26;3:305-316, 1999. © 1999 Elsevier Science Inc. All rights reserved.

To establish quantitative standards for the directionally averaged water apparent diffusion coefficient (D) and quantitative diffusion anisotropy (A sigma) of normal brains in newborns by using diffusion tensor magnetic resonance (MR) imaging.Diffusion tensor MR imaging was performed during the first 36 hours of life in 22 newborns (gestational age range, 31-41 weeks). Values of D and A sigma were measured in regions of interest chosen in the cortical gray matter, centrum semiovale, caudate nuclei, lentiform nuclei, thalami, internal capsules, and cerebellar hemispheres.The D values in the gray and white matter in newborns are considerably higher than those in adults. There is a striking correlation between gestational age and D, with D decreasing as gestational age increases. The A sigma values in the white matter in newborns are lower than those in adults. Values of A sigma show statistically significant correlations with gestational age only in the white matter of the centrum semiovale, in which A sigma values increase sharply near term.The D values primarily reflect overall brain water content. The A sigma values are more sensitive to tissue microstructure (e.g., white matter packing and myelination). The D and A sigma images reveal information and not apparent on T1- and T2-weighted images.

ARTICLE Sir, Jech et al. (2013) report that l-DOPA increased functional connectivity in the cerebellum and brainstem of patients with moderately severe Parkinson’s disease. This result is broadly complementary to our recent demonstration that functional connectivity between the striatum and a large region encompassing brainstem and cerebellum is abnormally decreased in advanced Parkinson’s disease compared with age-matched control subjects, despite continued treatment with l-DOPA (Hacker et al. , 2012). Whereas Jech et al. (2013) did not compare patients with Parkinson’s disease to control subjects, we did not study the effects of …

Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related 'mild' traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation.

This chapter presents a mathematical analysis of common modality image registration. Two alternative formulas are compared for computing registration error, the basis of these being the computation of image differences versus ratios. The theory suggests that the difference image method should be numerically more stable as well as more immune to noise. To test the theory, a Hoffman brain phantom is repeatedly scanned in one position, and images of variable statistical quality and spatial frequency content are prepared. These data are then submitted for realignment according to either the difference or the ratio image method. The difference image error function yielded consistently better precision in all but the most blurred data, in which case the two methods performed comparably. The precision advantage of the difference image method was attributable mainly to better determination of angular registration error as a consequence of reduced sensitivity to noise, and therefore greater tolerance of increased spatial frequency bandwidth. These results indicate that a modest improvement in realignment precision can be achieved by the use of error functions based on image differences as opposed to ratios.

To the Editor: Back et al1 recently reported apparent diffusion coefficient (ADC) measurements in acute stroke, finding no ADC fluctuations in peri-infarct regions over a 15-minute period. The reported data are convincing with regard to the temporal stability of infarct area within the 15-minute time window studied. We wish to address the issue of ADC spatial heterogeneity in stroke, specifically the authors’ contention that “there was a gradient of ADC reduction from the infarct periphery toward the infarct core.” They conclude that “this observation supports the view that the ischemia-induced early change in ADC is a blood flow-dependent event which reflects the severity (and duration) of the perfusion deficit.” As the authors have noted, this core-versus-periphery distinction in diffusion imaging has been previously advanced and is commonly accepted by the community of stroke researchers. However, it …

Steady-state scalp evoked potentials were recorded in response to amplitude modulated vibration applied to the fingers and palmar surface of one hand. Evoked response dependence on the frequency of amplitude modulation in the 2-40 Hz range was studied in a group of normal young adult volunteers. Response amplitude was greatest at low amplitude modulation frequencies. The greatest signal to EEG noise ratios were found at modulation frequencies near 26 Hz. At modulation frequencies near 26 Hz the steady-state response latency was found to be 58 +/- 14 msec. Inverse dipole modeling localized the steady-state evoked response generators in or near somatosensory cortex with the dipole moment orientation being predominantly in the anterior-posterior direction.

Brain atrophy has been reported in a number of MR studies of aging leg ‘) *’ Importantly, age-related alterations in regional volumes . have been correlated with performance on neuropsychological and experimental cognitive tasks ‘3, 41. Thus, changes in cortical morphology may have clinical significance. Similarly, understanding patterns of regional degeneration in the brain may aid in distinguishing between normal aging and preclinical dementia. Volumetric studies have provided valuable information on changes in the brain associated with aging “I. Still, few studies have examined changes over the entire cortex due to the labor-intensive nature of such measurements. We employed measurements of cortical thickness “’ based on accurate, automated reconstmctions of the brain from MR scans 16. ‘I allowing visualization of change across the complete cortical surface. Methods Structural MR scans were obtained from younger (YP; n = 19; mean age = 23.6, 18-31; 9MllOF) and older participants (OP; n = 10; mean age = 75.9.66-89; 3M/7F). All participants were nondemented (CDR = 0). YP were recruited from the Washington University community. OP were recruited through the Washington University Alzheimer’s Disease Center. OP were excluded if they had a history of neurologic, psychiatric, or medical illness that could contribute to dementia. Two to four MP-RAGE scans were averaged per participant (Siemens 1.5-T Vision System, resolution 1 X 1 X 1.25 mm, TR = 9.7ms, TE = 4ms, FA = lo”, TI = 20ms, TD = 500ms). Thickness measurements were obtained by reconstructing representations of the gray/white matter boundary and the cortical surface and then calculating the minimal distance between those two surfaces for each point on the gray/white matter boundary “I. Thickness maps were averaged across participants using a spherical morph to align cortical folding “I. ReSUltS Preliminary results suggested OP had significantly thinner cortex bilaterally in regions including the prefrontal cortex (near Brodmann Area [BA] 44), pre/postcentral regions (near BA 4/6), parietal (near BA 40/39), and occipital cortex (near BA 17/18) with a relative sparing of superior prefrontal cortex (e.g. near BA 8/9) and temporal lobes. The figure shows regions of statistically thinner cortex in OP with red to yellow indicating less to greater significance, respectively). Differences were preliminarily estimated between -0.25 to 0.50 mm. Aging is accompanied by thickness changes in prefrontal, somatosensory and occipital cortex. These conclusions must be considered with caution as there are potential confounds. Importantly, changes in tissue signal properties in aging and disease may contaminate measures of thickness. Additionally, larger groups of matched subjects should be examined. Nonetheless, these preliminary results suggest great promise for using cortical thickness measures to detect preclinical dementia and anatomic changes associated with cognitive decline [91.

Objective: To determine whether patients with blepharospasm have abnormal sensorimotor processing similar to patients with writer’s cramp. Background: Blepharospasm is a focal dystonia manifest by involuntary, excessive blinking and squeezing of the eyes. Altered sensorimotor processing may contribute to the development of dystonic movements. Previously the authors demonstrated decreased vibration-induced cortical blood flow responses in hand primary sensorimotor area (PSA) in patients with hand dystonia. Methods: In this prospective, case–control study, seven patients with blepharospasm were compared with seven normal subjects. PET measurements of regional blood flow were obtained using bolus administration of H 2 15 O at rest or during sequential vibration of either the left or the right hand or side of the mouth. Results: PSA activation decreased significantly in the patients with blepharospasm both ipsilateral (−68%; p = 0.0004) and contralateral to the side of facial stimulation (−56%; p = 0.0009). Patients had a 31% lower mean contralateral PSA response to hand vibration and a 51% smaller right supplementary motor area response to left-hand vibration than normal subjects, but these differences did not reach statistical significance. Conclusions: Patients with blepharospasm have abnormal sensorimotor processing in response to lower face vibration. They may also have abnormal brain responses to stimulation of clinically uninvolved parts of the body, but this requires confirmation.

SummaryCognitive decline is commonly observed in advanced aging even in the absence of disease. Here we explore the possibility that normal aging is accompanied by disruptive alterations in the coordination of large-scale brain systems that support high-level cognition. In 93 adults aged 18 to 93, we demonstrate that aging is characterized by marked reductions in normally present functional correlations within two higher-order brain systems. Anterior to posterior components within the default network were most severely disrupted with age. Furthermore, correlation reductions were severe in older adults free from Alzheimer's disease (AD) pathology as determined by amyloid imaging, suggesting that functional disruptions were not the result of AD. Instead, reduced correlations were associated with disruptions in white matter integrity and poor cognitive performance across a range of domains. These results suggest that cognitive decline in normal aging arises from functional disruption in the coordination of large-scale brain systems that support cognition.

SummarySpatial neglect is a syndrome following stroke manifesting attentional deficits in perceiving and responding to stimuli in the contralesional field. We examined brain network integrity in patients with neglect by measuring coherent fluctuations of fMRI signals (functional connectivity). Connectivity in two largely separate attention networks located in dorsal and ventral frontoparietal areas was assessed at both acute and chronic stages of recovery. Connectivity in the ventral network, part of which directly lesioned, was diffusely disrupted and showed no recovery. In the structurally intact dorsal network, interhemispheric connectivity in posterior parietal cortex was acutely disrupted but fully recovered. This acute disruption, and disrupted connectivity in specific pathways in the ventral network, strongly correlated with impaired attentional processing across subjects. Lastly, disconnection of the white matter tracts connecting frontal and parietal cortices was associated with more severe neglect and more disrupted functional connectivity. These findings support a network view in understanding neglect.

Summary Aerobic glycolysis (AG; i.e., nonoxidative metabolism of glucose despite the presence of abundant oxygen) accounts for 10%–12% of glucose used by the adult human brain. AG varies regionally in the resting state. Brain AG may support synaptic growth and remodeling; however, data supporting this hypothesis are sparse. Here, we report on investigations on the role of AG in the human brain. Meta-analysis of prior brain glucose and oxygen metabolism studies demonstrates that AG increases during childhood, precisely when synaptic growth rates are highest. In resting adult humans, AG correlates with the persistence of gene expression typical of infancy (transcriptional neoteny). In brain regions with the highest AG, we find increased gene expression related to synapse formation and growth. In contrast, regions high in oxidative glucose metabolism express genes related to mitochondria and synaptic transmission. Our results suggest that brain AG supports developmental processes, particularly those required for synapse formation and growth.

Traumatic axonal injury (TAI) is a major contributor to adverse outcomes following traumatic brain injury (TBI). Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique, which provides a robust measure of white matter integrity in patients with TBI. Certain brain regions have been identified as particularly susceptible to TAI by means of DTI. Few studies, however, have focused on describing the distribution of DTI abnormalities in individual TBI patients. The aim of this project was to conduct an exploratory analysis of the extent and distribution of axonal injury in TBI patients at a singlesubject level.