Peter W. R. Woodruff

Generic brain activation mapping in functional magnetic resonance imaging : A nonparametric approach

We report a novel method to identify brain regions generically activated by periodic experimental design in functional magnetic resonance imaging data. This involves: 1) registering each of N individual functional magnetic resonance imaging datasets in a standard space; 2) computing the median standardised power of response to the experimental design; 3) testing median standardised power at each voxel against its nonparametrically ascertained distribution under the null hypothesis of no experimental effect; and 4) constructing a generic brain activation map. The method is validated by analysis of 6 null images, acquired under conditions when the null hypothesis was known to be true; 8 images acquired during periodic auditory-verbal stimulation; and 6 images acquired during periodic performance of a covert verbal fluency task.

Response inhibition and impulsivity: an fMRI study

Aggressive, suicidal and violent behaviour have been associated with impulsive personality and difficulty in inhibiting responses. We used functional magnetic resonance imaging (fMRI) of the whole brain to examine the neural correlates of response inhibition in 19 normal subjects as they performed a Go/NoGo task. Subjects completed Eysencks Impulsivity Scale, Barratts Impulsivity Scale (BIS) and behavioural impulsivity tasks. Associations between blood oxygen level dependent (BOLD) response, trait impulsivity, task performance and National Adult Reading Test (NART) IQ were investigated. Neural response during response inhibition was most prominent in the right lateral orbitofrontal cortex. Responses were also seen in superior temporal gyrus, medial orbitofrontal cortex, cingulate gyrus, and inferior parietal lobule, predominantly on the right side. Subjects with greater scores on impulsivity scales and who made more errors had greater activation of paralimbic areas during response inhibition, while less impulsive individuals and those with least errors activated higher order association areas. Exploratory factor analysis of orbital activations, personality measures and errors of commission did not reveal a unitary dimension of impulsivity. However, the strong association between posterior orbital activation and Eysencks impulsivity score on a single factor suggests that greater engagement of right orbitofrontal cortex was needed to maintain behavioural inhibition in impulsive individuals. Lower IQ was more important than impulsivity scores in determining errors of commission during the task. Neuroimaging of brain activity during the Go/NoGo task may be useful in understanding the functional neuroanatomy and associated neurochemistry of response inhibition. It may also allow study of the effects of physical and psychological interventions on response inhibition in clinical conditions such as antisocial personality disorder.

Behavioural and functional anatomical correlates of deception in humans

Brain activity in humans telling lies has yet to be elucidated. We developed an objective approach to its investigation, utilizing a computer-based interrogation and fMRI. Interrogatory questions probed recent episodic memory in 30 volunteers studied outside and 10 volunteers studied inside the MR scanner. In a counter-balanced design subjects answered specified questions both truthfully and with lies. Lying was associated with longer response times (p < 0.001) and greater activity in bilateral ventrolateral prefrontal cortices (p < 0.05, corrected). These findings were replicated using an alternative protocol. Ventrolateral prefrontal cortex may be engaged in generating lies or withholding the truth.

The anatomy of conscious vision: an fMRI study of visual hallucinations

Despite recent advances in functional neuroimaging, the apparently simple question of how and where we see—the neurobiology of visual consciousness—continues to challenge neuroscientists. Without a method to differentiate neural processing specific to consciousness from unconscious afferent sensory signals, the issue has been difficult to resolve experimentally. Here we use functional magnetic resonance imaging (fMRI) to study patients with the Charles Bonnet syndrome, for whom visual perception and sensory input have become dissociated. We found that hallucinations of color, faces, textures and objects correlate with cerebral activity in ventral extrastriate visual cortex, that the content of the hallucinations reflects the functional specializations of the region and that patients who hallucinate have increased ventral extrastriate activity, which persists between hallucinations.

Investigating the functional anatomy of empathy and forgiveness

Previous functional brain imaging studies suggest that the ability to infer the intentions and mental states of others (social cognition) is mediated by medial prefrontal cortex. Little is known about the anatomy of empathy and forgiveness. We used functional MRI to detect brain regions engaged by judging others’ emotional states and the forgivability of their crimes. Ten volunteers read and made judgements based on social scenarios and a high level baseline task (social reasoning). Both empathic and forgivability judgements activated left superior frontal gyrus, orbitofrontal gyrus and precuneus. Empathic judgements also activated left anterior middle temporal and left inferior frontal gyri, while forgivability judgements activated posterior cingulate gyrus. Empathic and forgivability judgements activate specific regions of the human brain, which we propose contribute to social cohesion.

Investigation of facial recognition memory and happy and sad facial expression perception: an fMRI study

We investigated facial recognition memory (for previously unfamiliar faces) and facial expression perception with functional magnetic resonance imaging (fMRI). Eight healthy, right-handed volunteers participated. For the facial recognition task, subjects made a decision as to the familiarity of each of 50 faces (25 previously viewed; 25 novel). We detected signal increase in the right middle temporal gyrus and left prefrontal cortex during presentation of familiar faces, and in several brain regions, including bilateral posterior cingulate gyri, bilateral insulae and right middle occipital cortex during presentation of unfamiliar faces. Standard facial expressions of emotion were used as stimuli in two further tasks of facial expression perception. In the first task, subjects were presented with alternating happy and neutral faces; in the second task, subjects were presented with alternating sad and neutral faces. During presentation of happy facial expressions, we detected a signal increase predominantly in the left anterior cingulate gyrus, bilateral posterior cingulate gyri, medial frontal cortex and right supramarginal gyrus, brain regions previously implicated in visuospatial and emotion processing tasks. No brain regions showed increased signal intensity during presentation of sad facial expressions. These results provide evidence for a distinction between the neural correlates of facial recognition memory and perception of facial expression but, whilst highlighting the role of limbic structures in perception of happy facial expressions, do not allow the mapping of a distinct neural substrate for perception of sad facial expressions.

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.

Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder

BACKGROUND Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD.

Social cognition, brain networks and schizophrenia.

BACKGROUND A better understanding of the neural basis of social cognition including mindreading (or theory of mind) and empathy might help to explain some deficits in social functioning in people with schizophrenia. Our aim was to review neuroimaging and neuropsychological studies on social cognition, as they may shed light on the neural mechanisms of social cognition and its dysfunction in patients with schizophrenia. METHOD A selective literature review was undertaken. RESULTS Neuroimaging and neuropsychological studies suggest convergence upon specific networks for mindreading and empathy (the temporal cortex, amygdala and the prefrontal cortex). The frontal lobe is likely to play a central role in enabling social cognition, but mindreading and empathic abilities may require relatively different weighting of subcomponents within the same frontal-temporal social cognition network. CONCLUSIONS Disturbances in social cognition may represent an abnormal interaction between frontal lobe and its functionally connected cortical and subcortical areas. Future studies should seek to explore the heterogeneity of social dysfunction within schizophrenia.

Modulation of auditory and visual cortex by selective attention is modality-dependent.

Using functional magnetic resonance imaging (fMRI), we investigated whether the response of auditory and visual cortex was modulated by attending selectively to either heard or seen numbers presented simultaneously. Alternating attention between modalities modulated fMRI signal within the corresponding sensory cortex. This study provides evidence that attention acts locally during early auditory cognitive sensory processing, and that modulation of auditory and visual sensory cortex by attention is modality-dependent.