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Biomedical subjects

A M Dale

Publications and source records attributed to A M Dale.

At least 19 recordsLinked to original sources

Early-childhood temperament trajectories map onto transdiagnostic psychiatric risk.

Early-childhood temperament is associated with later mental health. Temperament continues to develop throughout the first years of life, and a single assessment cannot capture its trajectory. Whether departures from an individual's developmental trajectory carry psychiatric risk remains unknown. Using data from more than 50,000 children in the Norwegian Mother, Father and Child Cohort Study, we modeled longitudinal temperament at 1.5, 3, and 5 years of age with the FEMA-Long mixed-effects framework. We then quantified each child's departures from their predicted trajectories. Multivariate analysis revealed two transdiagnostic dimensions linking trajectory departures to psychiatric diagnoses across childhood and adolescence. Higher scores on the first dimension were associated with an increased hazard of subsequent ADHD diagnosis (hazard ratio = 1.54), and higher scores on the second with an increased hazard of Asperger syndrome (hazard ratio = 1.64). To examine the genetic basis of these associations, we performed longitudinal GWAS of temperament and conjunctional FDR analysis to detect loci shared with the associated diagnoses. The effects of these loci changed across early childhood, with some strengthening and others attenuating with age. These findings show that departures from predicted temperament trajectories reflect transdiagnostic psychiatric risk with a shared genetic basis. Longitudinal, trajectory-based monitoring could help identify children at elevated psychiatric risk.

Journal Article↗

The value of multichannel MEG and EEG in the presurgical evaluation of 70 epilepsy patients.

OBJECTIVE: To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery. METHODS: Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers. RESULTS: MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients). CONCLUSION: Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.

Adolescent↗

Top-down facilitation of visual recognition.

Cortical analysis related to visual object recognition is traditionally thought to propagate serially along a bottom-up hierarchy of ventral areas. Recent proposals gradually promote the role of top-down processing in recognition, but how such facilitation is triggered remains a puzzle. We tested a specific model, proposing that low spatial frequencies facilitate visual object recognition by initiating top-down processes projected from orbitofrontal to visual cortex. The present study combined magnetoencephalography, which has superior temporal resolution, functional magnetic resonance imaging, and a behavioral task that yields successful recognition with stimulus repetitions. Object recognition elicited differential activity that developed in the left orbitofrontal cortex 50 ms earlier than it did in recognition-related areas in the temporal cortex. This early orbitofrontal activity was directly modulated by the presence of low spatial frequencies in the image. Taken together, the dynamics we revealed provide strong support for the proposal of how top-down facilitation of object recognition is initiated, and our observations are used to derive predictions for future research.

Cerebral Cortex↗

Neuroimaging H.M.: a 10-year follow-up examination.

In 1997, Corkin et al. described the anatomical boundaries of the amnesic patient H.M.'s surgical resection, based on a comprehensive analysis of magnetic resonance imaging (MRI) scans collected in 1992 and 1993 (Corkin et al. (1997) J Neurosci 17:3964-3979). We subsequently scanned H.M. on several occasions, employing more advanced data acquisition and analysis methods, and now describe additional details about his brain anatomy and pathology. This account combines results from high-resolution T1-weighted scans, which provide measures of cortical and subcortical morphometry, diffusion tensor images, which provide quantitative information about white matter microstructure and the anatomy of major fasciculi, and T2-weighted images, which highlight damage to deep white matter. We applied new MRI analysis techniques to these scans to assess the integrity of areas throughout H.M.'s brain. We documented a number of new changes, including cortical thinning, atrophy of deep gray matter structures, and a large volume of abnormal white matter and deep gray matter signal. Most of these alterations were not apparent in his prior scans, suggesting that they are of recent origin. Advanced age and hypertension likely contributed to these new findings.

Aged↗

3T phased array MRI improves the presurgical evaluation in focal epilepsies: a prospective study.

BACKGROUND: Although detection of concordant lesions on MRI significantly improves postsurgical outcomes in focal epilepsy (FE), many conventional MR studies remain negative. The authors evaluated the role of phased array surface coil studies performed at 3 Tesla (3T PA MRI). METHODS: Forty patients with medically intractable focal epilepsies were prospectively imaged with 3T PA-MRI including high matrix TSE T2, fluid attenuated inversion recovery, and magnetization prepared rapid gradient echo. All patients were considered candidates for epilepsy surgery. 3T PA-MRIs were reviewed by a neuroradiologist experienced in epilepsy imaging with access to clinical information. Findings were compared to reports of prior standard 1.5T MRI epilepsy studies performed at tertiary care centers. RESULTS: Experienced, unblinded review of 3T PA-MRI studies yielded additional diagnostic information in 48% (19/40) compared to routine clinical reads at 1.5T. In 37.5% (15/40), this additional information motivated a change in clinical management. In the subgroup of patients with prior 1.5T MRIs interpreted as normal, 3T PA-MRI resulted in the detection of a new lesion in 65% (15/23). In the subgroup of 15 patients with known lesions, 3T PA-MRI better defined the lesion in 33% (5/15). CONCLUSION: Phased array surface coil studies performed at 3 Tesla read by an experienced unblinded neuroradiologist can improve the presurgical evaluation of patients with focal epilepsy when compared to routine clinical 1.5T studies read at tertiary care centers.

Adolescent↗

Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method.

Infants with low birth weight are at increased risk of perinatal brain injury. Disruption of normal cortical development may have consequences for later motor, behavioural and cognitive development. The aim of this study was to measure cerebral cortical thickness, area and volume with an automated MRI technique in 15-year-old adolescents who had low birth weight. Cerebral MRI for morphometric analysis was performed on 50 very low birth weight (VLBW, birth weight </=1500 g), 49 term small for gestational age births (SGA, birth weight <10th percentile at term) and 58 control adolescents. A novel method of cortical surface models yielded measurements of cortical thickness and area for each subject's entire brain and computed cross-subject statistics based on cortical anatomy. The cortical surface models demonstrated regional thinning of the parietal, temporal and occipital lobes in the VLBW group, whereas regional thickening was demonstrated in the frontal and occipital lobes. The areas of change were greatest in those with the shortest gestational age at birth and lowest birth weight. Cortical surface area and cortical volume were lower in the VLBW than in the Control group. Within the VLBW group, there was an association between surface area and estimation of the intelligence quotient IQ (IQ(est)) and between cortical volume and IQ(est). Furthermore, cortical grey matter as a proportion of brain volume was significantly lower in the VLBW, but not in the SGA group compared with Controls. This observed reorganization of the developing brain offers a unique opportunity to investigate any relationship between changes in cortical anatomy and cognitive and social impairments, and the increase in psychiatric disorders that have been found in VLBW children and adolescents.

Adolescent↗

Age-related changes in prefrontal white matter measured by diffusion tensor imaging.

Age-related degeneration of brain white matter (WM) has received a great deal of attention, with recent studies demonstrating that such changes are correlated with cognitive decline and increased risk for the development of age-related neurodegenerative disease. Past studies have used magnetic resonance imaging (MRI) to measure the volume of normal and abnormal tissue signal as an index of tissue pathology. More recently, diffusion tensor MRI (DTI) has been employed to obtain regional measures of tissue microstructure, such as fractional anisotropy (FA), providing better spatial resolution and potentially more sensitive metrics of tissue damage than traditional volumetric measures. We used DTI to examine the regional basis of age-related alterations in prefrontal WM. As expected from prior volumetric and DTI studies, prefrontal FA was reduced in older adults (OA) compared to young adults (YA). Although WM volume has been reported to be relatively preserved until late aging, FA was significantly reduced by middle age. Much of prefrontal WM showed reduced FA with increasing age. Ventromedial and deep prefrontal regions showed a somewhat greater reduction compared to other prefrontal areas. Prefrontal WM anisotropy correlated with prefrontal WM volume, but the correlation was significant only when the analysis was limited to participants over age 40. This evidence of widespread and regionally accelerated alterations in prefrontal WM with aging illustrates FA's potential as a microstructural index of volumetric measures.

Adult↗

Age-related alterations in white matter microstructure measured by diffusion tensor imaging.

Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration. Regional FA measures were estimated from nine regions of interest in each hemisphere and from the genu and splenium of the corpus callosum (CC). The results showed significant age-related decline in FA in frontal WM, the posterior limb of the internal capsule (PLIC), and the genu of the CC. In contrast, temporal and posterior WM was relatively preserved. These findings suggest that WM alterations are variable throughout the brain and that particular fiber populations within prefrontal region and PLIC are most vulnerable to age-related degeneration.

Adult↗

Size does matter in the long run: hippocampal and cortical volume predict recall across weeks.

OBJECTIVE: To study the morphometric determinants of recall of verbal material for an extended period in an adult lifespan sample. METHODS: Healthy adults of varying ages were studied using automated segmentation of MRI scans with volumes of hippocampus, cortex, and white matter, and verbal memory tests assessing recall after 5 minutes, 30 minutes, and a mean period of 11 weeks. Stepwise regression analyses were performed with 5 minutes, 30 minutes, and 11-week recall as the dependent variables. Hippocampal, cortical, and white matter volumes were included in the initial set of predictor variables in each case, and the analyses were repeated with age as an additional predictor variable. RESULTS: When age was not included, cortical volume was the only variable predicting recall after 5 and 30 minutes, whereas hippocampal and cortical volumes predicted recall after 11 weeks. When age was included in the model, this was the only variable predicting recall after 5 and 30 minutes, whereas age and hippocampus gave contributions in prediction of recall after several weeks. CONCLUSION: This study supports a critical role of cortical and hippocampal size in recall. Hippocampal size seems more important in recall after 11 weeks than after a shorter time interval.

Adult↗

A hybrid approach to the skull stripping problem in MRI.

We present a novel skull-stripping algorithm based on a hybrid approach that combines watershed algorithms and deformable surface models. Our method takes advantage of the robustness of the former as well as the surface information available to the latter. The algorithm first localizes a single white matter voxel in a T1-weighted MRI image, and uses it to create a global minimum in the white matter before applying a watershed algorithm with a preflooding height. The watershed algorithm builds an initial estimate of the brain volume based on the three-dimensional connectivity of the white matter. This first step is robust, and performs well in the presence of intensity nonuniformities and noise, but may erode parts of the cortex that abut bright nonbrain structures such as the eye sockets, or may remove parts of the cerebellum. To correct these inaccuracies, a surface deformation process fits a smooth surface to the masked volume, allowing the incorporation of geometric constraints into the skull-stripping procedure. A statistical atlas, generated from a set of accurately segmented brains, is used to validate and potentially correct the segmentation, and the MRI intensity values are locally re-estimated at the boundary of the brain. Finally, a high-resolution surface deformation is performed that accurately matches the outer boundary of the brain, resulting in a robust and automated procedure. Studies by our group and others outperform other publicly available skull-stripping tools.

Algorithms↗

Regional and progressive thinning of the cortical ribbon in Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a fatal and progressive neurodegenerative disease that is accompanied by involuntary movements, cognitive dysfunction, and psychiatric symptoms. Although progressive striatal degeneration is known to occur, little is known about how the disease affects the cortex, including which cortical regions are affected, how degeneration proceeds, and the relationship of the cortical degeneration to clinical symptoms. The cortex has been difficult to study in neurodegenerative diseases primarily because of its complex folding patterns and regional variability; however, an understanding of how the cortex is affected by the disease may provide important new insights into it. METHODS: Novel automated surface reconstruction and high-resolution MR images of 11 patients with HD and 13 age-matched subjects were used to obtain cortical thickness measurements. The same analyses were performed on two postmortem brains to validate these methods. RESULTS: Regionally specific heterogeneous thinning of the cortical ribbon was found in subjects with HD. Thinning occurred early, differed among patients in different clinical stages of disease, and appeared to proceed from posterior to anterior cortical regions with disease progression. The sensorimotor region was statistically most affected. Measurements performed on MR images of autopsy brains analyzed similarly were within 0.25 mm of those obtained using traditional neuropathologic methods and were statistically indistinguishable. CONCLUSIONS: The authors propose that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD. These measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications.

Adult↗

Conductivity tensor mapping of the human brain using diffusion tensor MRI.

Knowledge of the electrical conductivity properties of excitable tissues is essential for relating the electromagnetic fields generated by the tissue to the underlying electrophysiological currents. Efforts to characterize these endogenous currents from measurements of the associated electromagnetic fields would significantly benefit from the ability to measure the electrical conductivity properties of the tissue noninvasively. Here, using an effective medium approach, we show how the electrical conductivity tensor of tissue can be quantitatively inferred from the water self-diffusion tensor as measured by diffusion tensor magnetic resonance imaging. The effective medium model indicates a strong linear relationship between the conductivity and diffusion tensor eigenvalues (respectively, final sigma and d) in agreement with theoretical bounds and experimental measurements presented here (final sigma/d approximately 0.844 +/- 0.0545 S small middle dots/mm(3), r(2) = 0.945). The extension to other biological transport phenomena is also discussed.

Brain↗

Spatiotemporal maps of brain activity underlying word generation and their modification during repetition priming.

Spatiotemporal maps of brain activity based on magnetoencephalography were used to observe sequential stages in language processing and their modification during repetition priming. Subjects performed word-stem completion and produced either novel or repeated (primed) words across trials. Activation passes from primary visual cortex (activated at approximately 100 msec after word presentation), to left anteroventral occipital ( approximately 180 msec), to cortex in and near Wernicke's ( approximately 210 msec) and then Broca's ( approximately 370 msec) areas. In addition, a posteroventral temporal area is activated simultaneously with posterosuperior temporal cortex. This area shows an early ( approximately 200-245 msec) increase in activation to repeated word stems. In contrast, prefrontal and anterior temporal regions showed activity reductions to repeated word stems late ( approximately 365-500 msec) in processing. These results tend to support classical models of language and suggest that an effect of direct item repetition is to allow word-form processing to increase its contribution to task performance while concurrently allowing reductions in time-consuming frontal temporal processing.

Brain↗

Local and global attention are mapped retinotopically in human occipital cortex.

Clinical evidence suggests that control mechanisms for local and global attention are lateralized in the temporal-parietal cortex. However, in the human occipital (visual) cortex, the evidence for lateralized local/global attention is controversial. To clarify this matter, we used functional MRI to map activity in the human occipital cortex, during local and global attention, with sustained visual fixation. Data were analyzed in a flattened cortical format, relative to maps of retinotopy and spatial frequency peak tuning. Neither local nor global attention was lateralized in the occipital cortex. Instead, local attention and global attention appear to be special cases of visual spatial attention, which are mapped consistently with the maps of retinotopy and spatial frequency tuning, in multiple visual cortical areas.

Attention↗

Spatiotemporal brain imaging of visual-evoked activity using interleaved EEG and fMRI recordings.

Combined analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has the potential to provide higher spatiotemporal resolution than either method alone. In some situations, in which the activity of interest cannot be reliably reproduced (e.g., epilepsy, learning, sleep states), accurate combined analysis requires simultaneous acquisition of EEG and fMRI. Simultaneous measurements ensure that the EEG and fMRI recordings reflect the exact same brain activity state. We took advantage of the spatial filtering properties of the bipolar montage to allow recording of very short (125--250 ms) visual-evoked potentials (VEPs) during fMRI. These EEG and fMRI measurements are of sufficient quality to allow source localization of the cortical generators. In addition, our source localization approach provides a combined EEG/fMRI analysis that does not require any manual selection of fMRI activations or placement of source dipoles. The source of the VEP was found to be located in the occipital cortex. Separate analysis of EEG and fMRI data demonstrated good spatial overlap of the observed activated sites. As expected, the combined EEG/fMRI analysis provided better spatiotemporal resolution than either approach alone. The resulting spatiotemporal movie allows for the millisecond-to-millisecond display of changes in cortical activity caused by visual stimulation. These data reveal two peaks in activity corresponding to the N75 and the P100 components. This type of simultaneous acquisition and analysis allows for the accurate characterization of the location and timing of neurophysiological activity in the human brain.

Adult↗

Cortical mechanisms specific to explicit visual object recognition.

The cortical mechanisms associated with conscious object recognition were studied using functional magnetic resonance imaging (fMRI). Participants were required to recognize pictures of masked objects that were presented very briefly, randomly and repeatedly. This design yielded a gradual accomplishment of successful recognition. Cortical activity in a ventrotemporal visual region was linearly correlated with perception of object identity. Therefore, although object recognition is rapid, awareness of an object's identity is not a discrete phenomenon but rather associated with gradually increasing cortical activity. Furthermore, the focus of the activity in the temporal cortex shifted anteriorly as subjects reported an increased knowledge regarding identity. The results presented here provide new insights into the processes underlying explicit object recognition, as well as the analysis that takes place immediately before and after recognition is possible.

Adult↗

Spatiotemporal mapping of brain activity by integration of multiple imaging modalities.

Functional magnetic resonance imaging (fMRI) and positron emission tomography measure local changes in brain hemodynamics induced by cognitive or perceptual tasks. These measures have a uniformly high spatial resolution of millimeters or less, but poor temporal resolution (about 1s). Conversely, electroencephalography (EEG) and magnetoencephalography (MEG) measure instantaneously the current flows induced by synaptic activity, but the accurate localization of these current flows based on EEG and MEG data alone remains an unsolved problem. Recently, techniques have been developed that, in the context of brain anatomy visualized with structural MRI, use both hemodynamic and electromagnetic measures to arrive at estimates of brain activation with high spatial and temporal resolution. These methods range from simple juxtaposition to simultaneous integrated techniques. Their application has already led to advances in our understanding of the neural bases of perception, attention, memory and language. Further advances in multi-modality integration will require an improved understanding of the coupling between the physiological phenomena underlying the different signal modalities.

Animals↗

Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex.

Highly accurate surface models of the cerebral cortex are becoming increasingly important as tools in the investigation of the functional organization of the human brain. The construction of such models is difficult using current neuroimaging technology due to the high degree of cortical folding. Even single voxel misclassifications can result in erroneous connections being created between adjacent banks of a sulcus, resulting in a topologically inaccurate model. These topological defects cause the cortical model to no longer be homeomorphic to a sheet, preventing the accurate inflation, flattening, or spherical morphing of the reconstructed cortex. Surface deformation techniques can guarantee the topological correctness of a model, but are time-consuming and may result in geometrically inaccurate models. In order to address this need we have developed a technique for taking a model of the cortex, detecting and fixing the topological defects while leaving that majority of the model intact, resulting in a surface that is both geometrically accurate and topologically correct.

Cerebral Cortex↗