Mick Brammer

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.

Progressive increase of frontostriatal brain activation from childhood to adulthood during event-related tasks of cognitive control

Higher cognitive inhibitory and attention functions have been shown to develop throughout adolescence, presumably concurrent with anatomical brain maturational changes. The relatively scarce developmental functional imaging literature on cognitive control, however, has been inconsistent with respect to the neurofunctional substrates of this cognitive development, finding either increased or decreased executive prefrontal function in the progression from childhood to adulthood. Such inconsistencies may be due to small subject numbers or confounds from age‐related performance differences in block design functional MRI (fMRI). In this study, rapid, randomized, mixed‐trial event‐related fMRI was used to investigate developmental differences of the neural networks mediating a range of motor and cognitive inhibition functions in a sizeable number of adolescents and adults. Functional brain activation was compared between adolescents and adults during three different executive tasks measuring selective motor response inhibition (Go/no‐go task), cognitive interference inhibition (Simon task), and attentional set shifting (Switch task). Adults compared with children showed increased brain activation in task‐specific frontostriatal networks, including right orbital and mesial prefrontal cortex and caudate during the Go/no‐go task, right mesial and inferior prefrontal cortex, parietal lobe, and putamen during the Switch task and left dorsolateral and inferior frontotemporoparietal regions and putamen during the Simon task. Whole‐brain regression analyses with age across all subjects showed progressive age‐related changes in similar and extended clusters of task‐specific frontostriatal, frontotemporal, and frontoparietal networks. The findings suggest progressive maturation of task‐specific frontostriatal and frontocortical networks for cognitive control functions in the transition from childhood to mid‐adulthood. Hum Brain Mapp, 2006.

Functional frontalisation with age: mapping neurodevelopmental trajectories with fMRI

The aim of this study was to investigate whether previously observed hypofrontality in adolescents with attention deficit-hyperactivity disorder (ADHD) during executive functioning [Rubia K, Overmeyer S, Taylor E, Brammer M, Williams S, Simmons A, Andrew C, Bullmore ET. Hypofrontality in attention deficit hyperactivity disorder during higher order motor control: a study using fMRI. Am J Psychiatry 1999;156(6):891-896] could be attributed to delayed maturation of frontal cortex. Brain activation of 17 healthy subjects, 9 adolescents and 8 young adults, during performance of a motor response inhibition task and a motor timing task was measured using functional magnetic resonance imaging (fMRI). The effect of age on brain activation was estimated, using the analysis of variance and regression, at both voxel and regional levels. In the delay task, superior performance in adults was paralleled by a significantly increased power of response in a network comprising prefrontal and parietal cortical regions and putamen. In the stop task, alternative neuronal routes--left hemispheric prefrontal regions in adults and right hemispheric opercular frontal cortex and caudate in adolescents--seem to have been recruited by the two groups for achieving comparable performances. A significant age effect was found for the prefrontal activation in both task, confirming the hypothesis of a dysmaturational pathogenesis for the hypofrontality in ADHD.

Explicit and Implicit Neural Mechanisms for Processing of Social Information From Facial Expressions: A Functional Magnetic Resonance Imaging Study

The processing of changing nonverbal social signals such as facial expressions is poorly understood, and it is unknown if different pathways are activated during effortful (explicit), compared to implicit, processing of facial expressions. Thus we used fMRI to determine which brain areas subserve processing of high‐valence expressions and if distinct brain areas are activated when facial expressions are processed explicitly or implicitly. Nine healthy volunteers were scanned (1.5T GE Signa with ANMR, TE/TR 40/3,000 ms) during two similar experiments in which blocks of mixed happy and angry facial expressions (“on” condition) were alternated with blocks of neutral faces (control “off” condition). Experiment 1 examined explicit processing of expressions by requiring subjects to attend to, and judge, facial expression. Experiment 2 examined implicit processing of expressions by requiring subjects to attend to, and judge, facial gender, which was counterbalanced in both experimental conditions. Processing of facial expressions significantly increased regional blood oxygenation level‐dependent (BOLD) activity in fusiform and middle temporal gyri, hippocampus, amygdalohippocampal junction, and pulvinar nucleus. Explicit processing evoked significantly more activity in temporal lobe cortex than implicit processing, whereas implicit processing evoked significantly greater activity in amygdala region. Mixed high‐valence facial expressions are processed within temporal lobe visual cortex, thalamus, and amygdalohippocampal complex. Also, neural substrates for explicit and implicit processing of facial expressions are dissociable: explicit processing activates temporal lobe cortex, whereas implicit processing activates amygdala region. Our findings confirm a neuroanatomical dissociation between conscious and unconscious processing of emotional information. Hum. Brain Mapping 9:93–105, 2000.

The neural correlates of anhedonia in major depressive disorder

BACKGROUND Anhedonia is a relative lack of pleasure in response to formerly rewarding stimuli. It is an important diagnostic feature of major depressive disorder (MDD), and predicts antidepressant efficacy. Understanding its neurobiological basis may help to target new treatments and predict treatment outcomes. Using a novel paradigm, we aimed to explore the correlations between anhedonia severity and magnitude of neural responses to happy and sad stimuli in regions previously implicated in studies of human reward processing and depressive anhedonia. METHODS Neural responses to happy and sad emotional stimuli (autobiographical prompts and mood congruent facial expressions) were measured using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in twelve MDD individuals with varying degrees of anhedonia. RESULTS In response to happy stimuli, anhedonia, but not depression severity per se, was positively and negatively correlated with ventromedial prefrontal cortex (VMPFC) and amygdala/ventral striatal activity, respectively. State anxiety independently contributed to a VMPFC-subcortical dissociation of response to happy (but not sad) stimuli, which was similar, but different, to anhedonia. CONCLUSIONS These findings suggest that anhedonia and state anxiety are associated with dysfunction within neural systems underlying the response to, and assessment of, the rewarding potential of emotive stimuli in MDD, and highlight the importance of employing a symptom-dimension-based approach in the examination of the neurobiology of depression.

Towards a functional neuroanatomy of self processing: effects of faces and words

We studied the neural correlates of self vs. non-self judgements using functional magnetic resonance imaging (fMRI). Individually tailored faces and personality trait words were used as stimuli in three experiments (exp.). In the first two experiments, brain activation was measured while subjects viewed morphed versions of either their own (self face exp.) or their partners face (partners face exp.), alternating in blocks with presentation of an unknown face. In the self face exp. right limbic areas (hippocampal formation, insula, anterior cingulate), the right middle temporal lobe, left inferior parietal and left prefrontal regions showed signal changes. In the partners face exp., only the right insula was activated. In the third exp., subjects made decisions about psychological trait adjectives previously categorized as describing their own attributes. Activation was present in the precuneus, the left parietal lobe, left insula/inferior frontal gyrus and the left anterior cingulate. A reaction time advantage was present when subjects responded to self-relevant words. The main area with signal changes during self-reference processing, regardless of the type of stimulus, was the left fusiform gyrus. The self-relevant stimuli engaged to a differential extent long term and working memory, semantic and emotional processes. We suggest that regions activated by these stimuli are engaged in self-processing.

How Good Is Good Enough in Path Analysis of fMRI Data

This paper is concerned with the problem of evaluating goodness-of-fit of a path analytic model to an interregional correlation matrix derived from functional magnetic resonance imaging (fMRI) data. We argue that model evaluation based on testing the null hypothesis that the correlation matrix predicted by the model equals the population correlation matrix is problematic because P values are conditional on asymptotic distributional results (which may not be valid for fMRI data acquired in less than 10 min), as well as arbitrary specification of residual variances and effective degrees of freedom in each regional fMRI time series. We introduce an alternative approach based on an algorithm for automatic identification of the best fitting model that can be found to account for the data. The algorithm starts from the null model, in which all path coefficients are zero, and iteratively unconstrains the coefficient which has the largest Lagrangian multiplier at each step until a model is identified which has maximum goodness by a parsimonious fit index. Repeating this process after bootstrapping the data generates a confidence interval for goodness-of-fit of the best model. If the goodness of the theoretically preferred model is within this confidence interval we can empirically say that the theoretical model could be the best model. This relativistic and data-based strategy for model evaluation is illustrated by analysis of functional MR images acquired from 20 normal volunteers during periodic performance (for 5 min) of a task demanding semantic decision and subvocal rehearsal. A model including unidirectional connections from frontal to parietal cortex, designed to represent sequential engagement of rehearsal and monitoring components of the articulatory loop, is found to be irrefutable by hypothesis-testing and within confidence limits for the best model that could be fitted to the data.

Recognizing one's own face

We report two studies of facial self-perception using individually tailored, standardized facial photographs of a group of volunteers and their partners. A computerized morphing procedure was used to merge each target face with an unknown control face. In the first set of experiments, a discrimination task revealed a delayed response time for the more extensively morphed self-face stimuli. In a second set of experiments, functional magnetic resonance imaging (fMRI) was used to measure brain activation while subjects viewed morphed versions of either their own or their partners face, alternating in blocks with presentation of an unknown face. When subjects viewed themselves (minus activation for viewing an unknown face), increased blood oxygenation was detected in right limbic (hippocampal formation, insula, anterior cingulate), left prefrontal cortex and superior temporal cortex. In the partner (versus unknown) experiment, only the right insula was activated. We suggest that a neural network involving the right hemisphere in conjunction with left-sided associative and executive regions underlies the process of visual self-recognition. Together, this combination produces the unique experience of self-awareness.

A direct demonstration of functional specialization within motion-related visual and auditory cortex of the human brain

BACKGROUND Physiological studies of the macaque brain have shown that there is a large expanse of visual cortex, the V5 complex, which is specialized for visual motion, and that several areas within V5 are specialized for different kinds of visual motion. In continuing work on motion-related visual cortex, we wished to chart the specialized visual motion areas in the human brain and to determine their anatomical relationship. Human subjects viewed different motion displays, and the cortical location of the increased activity produced by each stimulus was recorded. The technique of functional magnetic resonance imaging (fMRI) was used, in order to image the same subjects repeatedly. RESULTS We found that each of the three motion stimuli activated specific parts of the V5 complex. These sites of activation overlap with V5 and, to a smaller extent, with each other. Unexpectedly, the three motion stimuli also activated neighbouring, but nonoverlapping, regions of auditory cortex that are normally activated by the perception of speech. CONCLUSIONS The three sites of activation produced by the visual motion stimuli occupy adjacent territories within the V5 complex. Components of the V5 complex are specifically connected to regions within auditory cortex.

A Double Dissociation of Ventromedial Prefrontal Cortical Responses to Sad and Happy Stimuli in Depressed and Healthy Individuals

BACKGROUND The ventromedial prefrontal cortex (VMPFC) is a region implicated in the assessment of the rewarding potential of stimuli and may be dysfunctional in major depressive disorder (MDD). The few studies examining prefrontal cortical responses to emotive stimuli in MDD have indicated increased VMPFC responses to pleasant images but decreased responses to sad mood provocation when compared with healthy individuals. We wished to corroborate these results by examining neural responses to personally relevant happy and sad stimuli in MDD and healthy individuals within the same paradigm. METHODS Neural responses to happy and sad emotional stimuli (autobiographical memory prompts and congruent facial expressions) were measured using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in MDD (n = 12) and healthy (n = 12) individuals. RESULTS Increased and decreased responses in VMPFC were observed in MDD and healthy individuals, respectively, to happy stimuli, whereas the pattern was reversed for MDD and healthy individual responses to sad stimuli. These findings were not explained by medication effects in depressed individuals. CONCLUSIONS These findings indicate a double dissociation of the pattern of VMPFC response to happy and sad stimuli in depressed and healthy individuals and suggest abnormal reward processing in MDD.