Fernando Zelaya

Colored noise and computational inference in neurophysiological (fMRI) time series analysis: resampling methods in time and wavelet domains.

Even in the absence of an experimental effect, functional magnetic resonance imaging (fMRI) time series generally demonstrate serial dependence. This colored noise or endogenous autocorrelation typically has disproportionate spectral power at low frequencies, i.e., its spectrum is  f–1 ‐like. Various pre‐whitening and pre‐coloring strategies have been proposed to make valid inference on standardised test statistics estimated by time series regression in this context of residually autocorrelated errors. Here we introduce a new method based on random permutation after orthogonal transformation of the observed time series to the wavelet domain. This scheme exploits the general whitening or decorrelating property of the discrete wavelet transform and is implemented using a Daubechies wavelet with four vanishing moments to ensure exchangeability of wavelet coefficients within each scale of decomposition. For  f–1 ‐like or fractal noises, e.g., realisations of fractional Brownian motion (fBm) parameterised by Hurst exponent 0 < H < 1, this resampling algorithm exactly preserves wavelet‐based estimates of the second order stochastic properties of the (possibly nonstationary) time series. Performance of the method is assessed empirically using  f–1 ‐like noise simulated by multiple physical relaxation processes, and experimental fMRI data. Nominal type 1 error control in brain activation mapping is demonstrated by analysis of 13 images acquired under null or resting conditions. Compared to autoregressive pre‐whitening methods for computational inference, a key advantage of wavelet resampling seems to be its robustness in activation mapping of experimental fMRI data acquired at 3 Tesla field strength. We conclude that wavelet resampling may be a generally useful method for inference on naturally complex time series. Hum. Brain Mapping 12:61–78, 2001.

Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging

A NOVEL MRI METHOD diffusion tensor imaging—was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimers disease. Relative to normal controls, patients with probable Alzheimers disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum. By contrast, pyramidal tract integrity seemed unchanged. This novel finding is consistent with the clinical presentation of probable Alzheimers disease, in which global cognitive decline is a more prominent feature than motor disturbance.

PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans.

The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight. However, in the current ‘obesogenic’ human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans. Here we show, using functional magnetic resonance imaging, that peptide YY3–36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.

Distinct Roles of Prefrontal Cortical Subregions in the Iowa Gambling Task

The Iowa Gambling Task (IGT) assesses decision-making under initially ambiguous conditions. Neuropsychological and neuroimaging data suggest, albeit inconsistently, the involvement of numerous prefrontal cortical regions in task performance. To clarify the contributions of different prefrontal regions, we developed and validated a version of the IGT specifically modified for event-related functional magnetic resonance imaging. General decision-making in healthy males elicited activation in the ventromedial prefrontal cortex. Choices from disadvantageous versus advantageous card decks produced activation in the medial frontal gyrus, lateral orbitofrontal cortex (OFC), and insula. Moreover, activation in these regions, along with the pre-supplementary motor area (pre-SMA) and secondary somatosensory cortex, was positively associated with task performance. Lateral OFC and pre-SMA activation also showed a significant modulation over time, suggesting a role in learning. Striato-thalamic regions responded to wins more than losses. These results both replicate and add to previous findings and help to reconcile inconsistencies in neuropsychological data. They reveal that deciding advantageously under initially ambiguous conditions may require both continuous and dynamic processes involving both the ventral and dorsal prefrontal cortex.

Motor response suppression and the prepotent tendency to respond : a parametric fMRI study

In the present study we utilised functional magnetic resonance imaging (fMRI) to examine cerebral activation during performance of a classic motor task in which response suppression load was parametrically varied. Linear increases in activity were observed in a distributed network of regions across both cerebral hemispheres, although with more extensive involvement of the right prefrontal cortex. Activated regions included prefrontal, parietal and occipitotemporal cortices. Decreasing activation was similarly observed in a distributed network of regions. These response forms are discussed in terms of an increasing requirement for visual cue discrimination and suppression/selection of motor responses, and a decreasing probability of the occurrence of non-target stimuli and attenuation of a prepotent tendency to respond. The results support recent proposals for a dominant role for the right-hemisphere in performance of motor response suppression tasks that emphasise the importance of the right prefrontal cortex.

Measuring fMRI reliability with the intra-class correlation coefficient.

The intra-class class correlation coefficient (ICC) is a prominent statistic to measure test-retest reliability of fMRI data. It can be used to address the question of whether regions of high group activation in a first scan session will show preserved subject differentiability in a second session. With this purpose, we present a method that extends voxel-wise ICC analysis. We show that voxels with high group activation have more probability of being reliable, if a subsequent session is performed, than typical voxels across the brain or across white matter. We also find that the existence of some voxels with high ICC but low group activation can be explained by stable signals across sessions that poorly fit the HRF model. At a region of interest level, we show that our voxel-wise ICC calculation is more robust than previous implementations under variations of smoothing and cluster size. The method also allows formal comparisons between the reliabilities of given brain regions; aimed at establishing which ROIs discriminate best between individuals. The method is applied to an auditory and a verbal working memory task. A reliability toolbox for SPM5 is provided at http://brainmap.co.uk.

Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers

BACKGROUND The neural correlates of anxiety associated with obsessive-compulsive symptomlike provocation in normal volunteers are unknown. METHODS Ten healthy volunteers participated in four functional magnetic resonance experiments. Subjects were scanned while viewing alternating blocks of emotional (normally aversive, washing-relevant, checking-relevant, or hoarding-relevant pictures) and neutral pictures, and imagining scenarios related to the content of each picture type. Nonparametric brain mapping analyses were used. RESULTS In response to the provocative pictures in all experiments, increases in subjective anxiety and activation in bilateral ventral prefrontal, limbic, dorsal prefrontal, and visual regions were demonstrated. Anxiety related to different symptom dimensions was associated with different patterns of activation: provocation of washing-relevant anxiety predominantly activated dorsal and ventral prefrontal regions; checking-relevant anxiety predominantly activated dorsal prefrontal regions; and hoarding-relevant anxiety predominantly activated ventral prefrontal regions and the left amygdala. CONCLUSIONS Our findings support a dimensional model of obsessive-compulsive disorder (OCD) whereby 1) the brain systems implicated in the mediation of anxiety in response to symptom-related material in normal subjects are similar to those identified in OCD patients during symptom provocation, and 2) anxiety associated with different symptom dimensions is associated with differential patterns of activation of these neural systems. Further investigation of the neural basis of OCD symptom dimensions is required.

AN EVALUATION OF THE TIME DEPENDENCE OF THE ANISOTROPY OF THE WATER DIFFUSION TENSOR IN ACUTE HUMAN ISCHEMIA

We have performed MRI examinations to determine the water diffusion tensor in the brain of six patients who were admitted to the hospital within 12 h after the onset of cerebral ischemic symptoms. The examinations have been carried out immediately after admission, and thereafter at varying intervals up to 90 days post admission. Maps of the trace of the diffusion tensor, the fractional anisotropy and the lattice index, as well as maps of cerebral blood perfusion parameters, were generated to quantitatively assess the character of the water diffusion tensor in the infarcted area. In patients with significant perfusion deficits and substantial lesion volume changes, four of six cases, our measurements show a monotonic and significant decrease in the diffusion anisotropy within the ischemic lesion as a function of time. We propose that retrospective analysis of this quantity, in combination with brain tissue segmentation and cerebral perfusion maps, may be used in future studies to assess the severity of the ischemic event.

Neural responses to dynamic expressions of fear in schizophrenia.

Abnormalities in social functioning are a significant feature of schizophrenia. One critical aspect of these abnormalities is the difficulty these individuals have with the recognition of facial emotions, particularly negative expressions such as fear. The present work focuses on fear perception and its relationship to the paranoid symptoms of schizophrenia, specifically, how underlying limbic system structures (i.e. the amygdala) react when probed with dynamic fearful facial expressions. Seven paranoid and eight non-paranoid subjects (all males) with a diagnosis of schizophrenia took part in functional magnetic resonance imaging study (1.5T) examining neural responses to emerging fearful expressions contrasted with dissipating fearful expressions. Subjects viewed emerging and dissipating expressions while completing a gender discrimination task. Their brain activation was compared to that of 10 healthy male subjects. Increased hippocampal activation was seen in the non-paranoid group, while abnormalities in the bilateral amygdalae were observed only in the paranoid individuals. These patterns may represent trait-related hippocampal dysfunction, coupled with state (specifically paranoia) related amygdala abnormalities. The findings are discussed in light of models of paranoia in schizophrenia.

Dehydration affects brain structure and function in healthy adolescents

It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross‐over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto‐parietal blood‐oxygen‐level‐dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo‐spatial processing. Hum Brain Mapp, 2010.