Author name cluster

Ben J. Harrison

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19 papers

1 author row

YNICL Journal 2024 Journal Article

Altered task-related decoupling of the rostral anterior cingulate cortex in depression

Christine A. Leonards
Ben J. Harrison
Alec J. Jamieson
James Agathos
Trevor Steward
Christopher G. Davey

Dysfunctional activity of the rostral anterior cingulate cortex (rACC) - an extensively connected hub region of the default mode network - has been broadly linked to cognitive and affective impairments in depression. However, the nature of aberrant task-related rACC suppression in depression is incompletely understood. In this study, we sought to characterize functional connectivity of rACC activity suppression ('deactivation') - an essential feature of rACC function - during external task engagement in depression. Specifically, we aimed to explore neural patterns of functional decoupling and coupling with the rACC during its task-driven suppression. We enrolled 81 15- to 25-year-old young people with moderate-to-severe major depressive disorder (MDD) before they commenced a 12-week clinical trial that assessed the effectiveness of cognitive behavioral therapy plus either fluoxetine or placebo. Ninety-four matched healthy controls were also recruited. Participants completed a functional magnetic resonance imaging face matching task known to elicit rACC suppression. To identify brain regions associated with the rACC during its task-driven suppression, we employed a seed-based functional connectivity analysis. We found MDD participants, compared to controls, showed significantly reduced 'decoupling' of the rACC with extended task-specific regions during task performance. Specifically, less decoupling was observed in the occipital and fusiform gyrus, dorsal ACC, medial prefrontal cortex, cuneus, amygdala, thalamus, and hippocampus. Notably, impaired decoupling was apparent in participants who did not remit to treatment, but not treatment remitters. Further, we found MDD participants showed significant increased coupling with the anterior insula cortex during task engagement. Our findings indicate that aberrant task-related rACC suppression is associated with disruptions in adaptive neural communication and dynamic switching between internal and external cognitive modes that may underpin maladaptive cognitions and biased emotional processing in depression.

YNIMG Journal 2023 Journal Article

Subcortical contributions to salience network functioning during negative emotional processing

Sevil Ince
Trevor Steward
Ben J. Harrison
Alec J. Jamieson
Christopher G. Davey
James A. Agathos
Bradford A. Moffat
Rebecca K. Glarin

Core regions of the salience network (SN), including the anterior insula (aINS) and dorsal anterior cingulate cortex (dACC), coordinate rapid adaptive changes in attentional and autonomic processes in response to negative emotional events. In doing so, the SN incorporates bottom-up signals from subcortical brain regions, such as the amygdala and periaqueductal gray (PAG). However, the precise influence of these subcortical regions is not well understood. Using ultra-high field 7-Tesla functional magnetic resonance imaging, this study investigated the bottom-up interactions of the amygdala and PAG with the SN during negative emotional salience processing. Thirty-seven healthy participants completed an emotional oddball paradigm designed to elicit a salient negative emotional response via the presentation of random, task-irrelevant negative emotional images. Negative emotional processing was associated with prominent activation in the SN, spanning the amygdala, PAG, aINS, and dACC. Consistent with previous research, analysis using dynamic causal modelling revealed an excitatory influence from the amygdala to the aINS, dACC, and PAG. In contrast, the PAG showed an inhibitory influence on amygdala, aINS and dACC activity. Our findings suggest that the amygdala may amplify the processing of negative emotional stimuli in the SN to enable upstream access to attentional resources. In comparison, the inhibitory influence of the PAG possibly reflects its involvement in modulating sympathetic-parasympathetic autonomic arousal mediated by the SN. This PAG-mediated effect may be driven by amygdala input and facilitate bottom-up processing of negative emotional stimuli. Overall, our results show that the amygdala and PAG modulate divergent functions of the SN during negative emotional processing.

YNIMG Journal 2022 Journal Article

Modulation of the brain's core-self network by self-appraisal processes

Rebekah Delahoy
Christopher G. Davey
Alec J. Jamieson
Laura Finlayson-Short
Hannah S. Savage
Trevor Steward
Ben J. Harrison

The 'core' regions of the default mode network (DMN) - the medial prefrontal cortex (MPFC), the posterior cingulate cortex (PCC), and inferior parietal lobules (IPL) - show consistent engagement across mental states that involve self-oriented processing. Precisely how these regions interact in support of such processes remains an important unanswered question. In the current functional magnetic resonance imaging (fMRI) study, we examined dynamic interactions of the 'core-self' DMN regions during two forms of self-referential cognition: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about oneself from a third-person perspective). One-hundred and eleven participants completed our dual self-appraisal task during fMRI, and general linear models were used to characterize common and distinct neural responses to these conditions. Informed by these results, we then applied dynamic causal modelling to examine causal interactions among the 'core-self' regions, and how they were specifically modulated under the influence of direct and reflected self-appraisal. As a primary observation, this network modelling revealed a distinct inhibitory influence of the left IPL on the PCC during reflected compared to direct self-appraisal, which was accompanied by evidence of greater activation in both regions during the reflected self-appraisal condition. We suggest that the greater engagement of posterior DMN regions during reflected self-appraisal is a function of the higher-order processing needed for this form of self-appraisal, with the left IPL supporting abstract self-related processes including episodic memory retrieval and shifts of perspective. Overall, we show that core DMN regions interact in functionally unique ways in support of self-referential processes, even when these processes are inter-related. Further characterization of DMN functional interactions across self-related mental states is likely to inform a deeper understanding of how this brain network orchestrates the self.

YNIMG Journal 2021 Journal Article

Neural mediators of subjective and autonomic responding during threat learning and regulation

Hannah S. Savage
Christopher G. Davey
Tor D. Wager
Sarah N. Garfinkel
Bradford A. Moffat
Rebecca K. Glarin
Ben J. Harrison

Threat learning elicits robust changes across multiple affective domains, including changes in autonomic indices and subjective reports of fear and anxiety. It has been argued that the underlying causes of such changes may be dissociable at a neural level, but there is currently limited evidence to support this notion. To address this, we examined the neural mediators of trial-by-trial skin conductance responses (SCR), and subjective reports of anxious arousal and valence in participants (n = 27; 17 females) performing a threat reversal task during ultra-high field functional magnetic resonance imaging. This allowed us to identify brain mediators during initial threat learning and subsequent threat reversal. Significant neural mediators of anxious arousal during threat learning included the dorsal anterior cingulate, anterior insula cortex (AIC), and ventromedial prefrontal cortex (vmPFC), subcortical regions including the amygdala, ventral striatum, caudate and putamen, and brain-stem regions including the pons and midbrain. By comparison, autonomic changes (SCR) were mediated by a subset of regions embedded within this broader circuitry that included the caudate, putamen and thalamus, and two distinct clusters within the vmPFC. The neural mediators of subjective negative valence showed prominent effects in posterior cortical regions and, with the exception of the AIC, did not overlap with threat learning task effects. During threat reversal, positive mediators of both subjective anxious arousal and valence mapped to the default mode network; this included the vmPFC, posterior cingulate, temporoparietal junction, and angular gyrus. Decreased SCR during threat reversal was positively mediated by regions including the mid cingulate, AIC, two sub-regions of vmPFC, the thalamus, and the hippocampus. Our findings add novel evidence to support distinct underlying neural processes facilitating autonomic and subjective responding during threat learning and threat reversal. The results suggest that the brain systems engaged in threat learning mostly capture the subjective (anxious arousal) nature of the learning process, and that appropriate responding during threat reversal is facilitated by participants engaging self- and valence-based processes. Autonomic changes (SCR) appear to involve distinct facilitatory and regulatory contributions of vmPFC sub-regions.

YNICL Journal 2021 Journal Article

Self-other referential neural processing in social anxiety disorder and major depressive disorder

Laura Finlayson-Short
Ben J. Harrison
Christopher Davey

BACKGROUND: Social anxiety disorder (SAD) and major depressive disorder (MDD) are highly comorbid and share impairments in self-referential and social processing. Many naturalistic judgements activate these processes concurrently, which can be referred to as "self-other referential processing". We sought to examine its neural correlates in young people with SAD and MDD using a novel experimental task. METHODS: Fifty six young people aged 16 to 25 with diagnoses of SAD and/or MDD (15 with SAD [M = 20.3 years, 60% female], 17 with MDD [M = 19.8 years, 53% female], 24 with comorbid SAD and MDD [M = 19.8 years, 67% female]) and 76 age and gender-matched healthy controls (HCs; M = 20.7 years, 66% female) completed a novel self-other referential processing fMRI task that involved rating how much one related to emotional faces in active conditions and judging how far apart each person's eyes were in control conditions. RESULTS: Participants with SAD had more and those with MDD had less activity in social cognitive areas than HCs when processing social information across all conditions and emotion types. Participants with comorbid SAD-MDD exhibited a distinct pattern of neural activity to patients with single diagnoses. Across the whole sample, the activation of reward system areas (the medial orbitofrontal cortex and caudate) in response to increasing relatedness correlated positively with a dimensional measure of social anxiety. CONCLUSIONS: Young people with SAD, MDD and comorbid SAD-MDD showed deficits in social processing, but they were not specifically related to self-other referential processing. Dimensional social anxiety symptoms were correlated with reward system activation, suggesting that such symptoms are associated with an overestimation of the hedonic value of social stimuli. These novel findings have implications for our understanding of the neural correlates of SAD and MDD, suggesting that alterations in social processing and reward functioning underlie the impairments in self and social processing that characterize both disorders.

YNIMG Journal 2020 Journal Article

Clarifying the neural substrates of threat and safety reversal learning in humans

Hannah S. Savage
Christopher G. Davey
Miquel A. Fullana
Ben J. Harrison

Responding flexibly to sources of threat and safety is critical to the adaptive regulation of emotions, including fear. At a neural systems level, such flexibility is thought to rely on an extended neural circuitry involving the dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortices (vmPFC), although precisely how this occurs remains unclear. Using a novel fear reversal task and functional magnetic resonance imaging (fMRI), we examined the neural correlates of threat and safety reversal learning and their associations with individual differences in anxious responding in a large sample of healthy adolescents and young adults. Overall, participants demonstrated successful threat and safety reversal learning, as indexed by subjective ratings. At a whole-brain level, threat reversal was associated with significant activation of the bilateral anterior insular cortex and dACC, in particular its rostral subregion. Conversely, safety reversal led to significant activation of the anterior vmPFC, together with posterior mid-line regions. Further analyses of regional responses suggested a more selective role for the rostral dACC in threat signal updating, as well as a direct association of its activity with participants' change in subjective anxious arousal to the reversed threat. Taken together, our findings complement existing neurocircuitry models of human fear regulation, particularly regarding the importance of midline cortical regions, and provide further insights into their specific contribution to flexible threat-safety signal processing. In particular, our results suggest that rostral dACC function may be more centrally involved in regulating levels of anxious arousal when flexibility is required. They also raise important questions regarding the vmPFC's role in safety learning, particularly involving its hypothesized subregional contributions to response inhibitory versus stimulus value processing functions.

YNIMG Journal 2019 Journal Article

Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits

Linden Parkes
Jeggan Tiego
Kevin Aquino
Leah Braganza
Samuel R. Chamberlain
Leonardo F. Fontenelle
Ben J. Harrison
Valentina Lorenzetti

Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients’ scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.

YNIMG Journal 2018 Journal Article

A common brain network among state, trait, and pathological anxiety from whole-brain functional connectivity

Yu Takagi
Yuki Sakai
Yoshinari Abe
Seiji Nishida
Ben J. Harrison
Ignacio Martínez-Zalacaín
Carles Soriano-Mas
Jin Narumoto

Anxiety is one of the most common mental states of humans. Although it drives us to avoid frightening situations and to achieve our goals, it may also impose significant suffering and burden if it becomes extreme. Because we experience anxiety in a variety of forms, previous studies investigated neural substrates of anxiety in a variety of ways. These studies revealed that individuals with high state, trait, or pathological anxiety showed altered neural substrates. However, no studies have directly investigated whether the different dimensions of anxiety share a common neural substrate, despite its theoretical and practical importance. Here, we investigated a brain network of anxiety shared by different dimensions of anxiety in a unified analytical framework using functional magnetic resonance imaging (fMRI). We analyzed different datasets in a single scale, which was defined by an anxiety-related brain network derived from whole brain. We first conducted the anxiety provocation task with healthy participants who tended to feel anxiety related to obsessive-compulsive disorder (OCD) in their daily life. We found a common state anxiety brain network across participants (1585 trials obtained from 10 participants). Then, using the resting-state fMRI in combination with the participants' behavioral trait anxiety scale scores (879 participants from the Human Connectome Project), we demonstrated that trait anxiety shared the same brain network as state anxiety. Furthermore, the brain network between common to state and trait anxiety could detect patients with OCD, which is characterized by pathological anxiety-driven behaviors (174 participants from multi-site datasets). Our findings provide direct evidence that different dimensions of anxiety have a substantial biological inter-relationship. Our results also provide a biologically defined dimension of anxiety, which may promote further investigation of various human characteristics, including psychiatric disorders, from the perspective of anxiety.

YNIMG Journal 2017 Journal Article

Human ventromedial prefrontal cortex and the positive affective processing of safety signals

Ben J. Harrison
Miquel Angel Fullana
Esther Via
Carles Soriano-Mas
Bram Vervliet
Ignacio Martínez-Zalacaín
Jesus Pujol
Christopher G. Davey

Human functional magnetic resonance imaging (fMRI) studies suggest that the ventromedial prefrontal cortex (vmPFC) contributes to the learned discrimination of threat and safety signals, although its precise contribution to these processes remains unclear. One hypothesis is that the vmPFC supports the positive affective processing of safety signals linked to their implicit stress-relieving properties. We set out to test this hypothesis and to examine the specificity of vmPFC responses to safety signal processing versus its high level of ‘default mode’ activity. Sixty participants completed an fMRI conditioning task that involved the generation of a conditioned threat (CS+) and safety (CS-) signal following the completion of a pre-conditioning baseline. Confirming past findings, activation of the vmPFC and other midline cortical and parietal areas – broadly resembling the default mode network – robustly discriminated between the CS- and CS+. However, when adjusting for this network's characteristic ‘baseline’ activity, only a subset of regions, including the vmPFC, was activated by the CS-. Regional selectivity for safety signal processing was confirmed by demonstrating a significant correlation between the magnitude of vmPFC responses and self-rated positive affect evoked by the CS-. Taken together, our current findings confirm a link between human vmPFC activity and the positive affective processing of safety signals. We discuss these findings with regards a broader model of human vmPFC function and its suggested higher-order contribution to emotionally adaptive behavior.

YNIMG Journal 2016 Journal Article

Mapping the self in the brain's default mode network

Christopher G. Davey
Jesus Pujol
Ben J. Harrison

The brain's default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. While the DMN is important for such processes, it has functions other than self-reference, and self-referential processes are supported by regions outside of the DMN. In our study of 88 participants, we examined self-referential and resting-state processes to clarify the extent to which DMN activity was common and distinct between the conditions. Within areas commonly activated by self-reference and rest we sought to identify those that showed additional functional specialization for self-referential processes: these being not only activated by self-reference and rest but also showing increased activity in self-reference versus rest. We examined the neural network properties of the identified ‘core-self’ DMN regions—in medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and inferior parietal lobule—using dynamic causal modeling. The optimal model identified was one in which self-related processes were driven via PCC activity and moderated by the regulatory influences of MPFC. We thus confirm the significance of these regions for self-related processes and extend our understanding of their functionally specialized roles.

YNIMG Journal 2015 Journal Article

Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory

Ian H. Harding
Murat Yücel
Ben J. Harrison
Christos Pantelis
Michael Breakspear

Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands; a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control.

YNICL Journal 2015 Journal Article

Specific functional connectivity alterations of the dorsal striatum in young people with depression

Rebecca Kerestes
Ben J. Harrison
Orwa Dandash
Katerina Stephanou
Sarah Whittle
Jesus Pujol
Christopher G. Davey

BACKGROUND: Altered basal ganglia function has been implicated in the pathophysiology of youth Major Depressive Disorder (MDD). Studies have generally focused on characterizing abnormalities in ventral "affective" corticostriatal loops supporting emotional processes. Recent evidence however, has implicated alterations in functional connectivity of dorsal "cognitive" corticostriatal loops in youth MDD. The contribution of dorsal versus ventral corticostriatal alterations to the pathophysiology of youth MDD remains unclear. METHODS: Twenty-one medication-free patients with moderate-to-severe MDD between the ages of 15 and 24 years old were matched with 21 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging we systematically investigated connectivity of eight dorsal and ventral subdivisions of the striatum. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the depressed and control groups. RESULTS: Depressed youths showed alterations in functional connectivity that were confined to the dorsal corticostriatal circuit. Compared to controls, depressed patients showed increased connectivity between the dorsal caudate nucleus and ventrolateral prefrontal cortex bilaterally. Increased depression severity correlated with the magnitude of dorsal caudate connectivity with the right dorsolateral prefrontal cortex. There were no significant between-group differences in connectivity of ventral striatal regions. CONCLUSIONS: The results provide evidence that alterations in corticostriatal connectivity are evident at the early stages of the illness and are not a result of antidepressant treatment. Increased connectivity between the dorsal caudate, which is usually associated with cognitive processes, and the more affectively related ventrolateral prefrontal cortex may reflect a compensatory mechanism for dysfunctional cognitive-emotional processing in youth depression.

YNIMG Journal 2014 Journal Article

Does motion-related brain functional connectivity reflect both artifacts and genuine neural activity?

Jesus Pujol
Dídac Macià
Laura Blanco-Hinojo
Gerard Martínez-Vilavella
Jordi Sunyer
Rafael de la Torre
Assumpta Caixàs
Rocío Martín-Santos

Imaging research on functional connectivity is uniquely contributing to characterize the functional organization of the human brain. Functional connectivity measurements, however, may be significantly influenced by head motion that occurs during image acquisition. The identification of how motion influences such measurements is therefore highly relevant to the interpretation of a study's results. We have mapped the effect of head motion on functional connectivity in six different populations representing a wide range of potential influences of motion on functional connectivity. Group-level voxel-wise maps of the correlation between a summary head motion measurement and functional connectivity degree were estimated in 80 young adults, 71 children, 53 older adults, 20 patients with Down syndrome, 24 with Prader–Willi syndrome and 20 with Williams syndrome. In highly compliant young adults, motion correlated with functional connectivity measurements showing a system-specific anatomy involving the sensorimotor cortex, visual areas and default mode network. Further characterization was strongly indicative of these changes expressing genuine neural activity related to motion, as opposed to pure motion artifact. In the populations with larger head motion, results were more indicative of widespread artifacts, but showing notably distinct spatial distribution patterns. Group-level regression of motion effects was efficient in removing both generalized changes and changes putatively related to neural activity. Overall, this study endorses a relatively simple approach for mapping distinct effects of head motion on functional connectivity. Importantly, our findings support the intriguing hypothesis that a component of motion-related changes may reflect system-specific neural activity.

YNICL Journal 2014 Journal Article

Functional brain imaging studies of youth depression: A systematic review

Rebecca Kerestes
Christopher G. Davey
Katerina Stephanou
Sarah Whittle
Ben J. Harrison

BACKGROUND: There is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD. METHODS: A literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13-18 and 19-25 years of age, respectively. RESULTS: Twenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in "extended medial network" regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition. CONCLUSIONS: Youth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression.

YNIMG Journal 2010 Journal Article

Dynamic assessment of the right lateral frontal cortex response to painful stimulation

Marina López-Solà
Jesus Pujol
Rosa Hernández-Ribas
Ben J. Harrison
Héctor Ortiz
Carles Soriano-Mas
Joan Deus
José M. Menchón

The lateral surface of the right frontal lobe has a relevant role in modulating behavioral responses to aversive stimuli and may significantly influence pain experience. Imaging studies suggest that this modulatory role is multifaceted, but no studies have assessed the regional specialization of this cortex on the basis of its response dynamics during pain processing. We aimed to investigate functional specialization within the right lateral frontal cortex using a dynamic fMRI approach. Brain responses to a mechanical painful stimulus and a preceding anticipatory cue (auditory tone) were assessed in 25 healthy subjects. Functional data were decomposed into 15 sequential activation maps covering the full anticipation-painful stimulation cycle using a finite impulse response (FIR) analysis approach. Movie sequences showing the temporal evolution of brain activation illustrate the findings. A region involving premotor–prefrontal cortices was activated soon after the anticipatory cue and showed a significant correlation with both anterior cingulate cortex activation and subjective pain ratings. The frontal operculum also showed a significant anticipatory response, but the most robust activation followed painful stimulation onset and was strongly correlated with insula activation. The anterior prefrontal cortex showed full activation during late painful stimulation and was negatively correlated with pain unpleasantness. In conclusion, different elements within the right lateral frontal cortex showed distinct activation dynamics in response to painful stimulation, which would suggest relevant regional specialization during pain processing. These findings are congruent with the broad functional role of the right frontal cortex and its influence on crucial aspects of human behavior.

YNIMG Journal 2007 Journal Article

Brain structural correlates of depressive comorbidity in obsessive–compulsive disorder

Narcís Cardoner
Carles Soriano-Mas
Jesús Pujol
Pino Alonso
Ben J. Harrison
Joan Deus
Rosa Hernández-Ribas
José M. Menchón

The high comorbidity of obsessive–compulsive disorder (OCD) with major depressive disorder (MDD) suggests common neurobiological substrates. We assessed the contribution of lifetime MDD to brain structural alterations in OCD using magnetic resonance imaging. OCD patients with (n =33) or without (n =39) lifetime MDD, and 72 control subjects were assessed. Comparative region of interest (ROI) analyses assessed the contribution of lifetime MDD to gray matter volume alterations in OCD patients. Interregional correlations of gray matter volume were also examined and voxelwise analyses were performed to identify alterations in other brain regions. OCD patients with lifetime MDD showed a larger reduction of medial orbitofrontal cortex (mOFC) gray matter volume. Both OCD groups showed distinct correlations of mOFC gray matter volume with other relevant brain regions. For patients with MDD, this involved the medial frontal gyrus, and right insula and amygdala regions, whereas for those OCD patients without MDD, the rostral anterior cingulate cortex was involved. Our findings support existing evidence suggesting a non-specific involvement of mOFC alterations in a range of neuropsychiatric disorders. Nevertheless, volume reduction in this region, together with an abnormal pattern of interregional correlations with other emotion-relevant brain areas, may contribute to explain the diathesis for MDD comorbidity in OCD.

YNIMG Journal 2007 Journal Article

Identifying patients with obsessive–compulsive disorder using whole-brain anatomy

Carles Soriano-Mas
Jesús Pujol
Pino Alonso
Narcís Cardoner
José M. Menchón
Ben J. Harrison
Joan Deus
Julio Vallejo

Structural neuroimaging studies have reported a variety of brain alterations between groups of obsessive–compulsive disorder (OCD) patients and healthy controls. However, the large heterogeneity in discrete anatomical measures that exists among patients prevents a clear discrimination of single patients from healthy subjects. This reduces the potential clinical applicability of structural neuroimaging studies. In the present study we assessed the feasibility of identifying OCD patients on the basis of whole-brain anatomical alterations. Whole-brain magnetic resonance images were collected from two consecutive samples of OCD outpatients (n =72 and n =30), and control subjects (n =72 and n =30). We computed the whole-brain (voxel-wise) pattern of structural difference between OCD patients and control subjects at the group level. A single expression value of this difference pattern was calculated for each subject, expressing their degree of ‘OCD-like’ anatomical alteration. Accuracy of patient classification based on these expression values was assessed using two validation approaches. Firstly, using a cross-validation method, we obtained a high classification accuracy (average of the sensitivity and specificity indices) of 93. 1%. In a second assessment, which classified new groups of OCD patients and control subjects, overall accuracy was lower at 76. 6%. Individual expression values for OCD patients were significantly correlated with overall symptom severity as measured by the Y-BOCS scale. Our results suggest that OCD patients can be identified on the basis of whole-brain structural alterations, although the accuracy of our approach may be limited by the inherent variability of psychiatric populations. Nevertheless, the anatomical characterization of individual patients may ultimately provide the psychiatrist with relevant biological information.

YNIMG Journal 2007 Journal Article

State, trait and biochemical influences on human anterior cingulate function

Murat Yücel
Ben J. Harrison
Stephen J. Wood
Alex Fornito
Kerrie Clarke
R. Mark Wellard
Sue Cotton
Christos Pantelis

The dorsal part of the human anterior cingulate cortex (dACC) is reliably activated in situations requiring cognitive control, especially during states of conflict. However, little is known about how individual differences in the neural characteristics of the dACC and major dimensions of behavior, affect this brain response. We recruited 28 healthy adults and employed a multi-modal neuroimaging approach combined with a task designed to specifically activate the human dACC and statistical path analysis to demonstrate clear roles for intelligence, personality and concentrations of neuronal N-acetylaspartate in determining dACC activation. These influences were comparable in magnitude to those associated with the experience of conflict. Our findings extend current understandings of the neural substrates of cognitive control by modeling the effect of neuronal viability, intelligence, and personality, on dACC activation. They also highlight the importance of considering enduring personal characteristics when mapping human brain–behavior relationships.

YNIMG Journal 2005 Journal Article

Functional connectivity during Stroop task performance

Ben J. Harrison
Marnie Shaw
Murat Yücel
Rosemary Purcell
Warrick J. Brewer
Stephen C. Strother
Gary F. Egan
James S. Olver

Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2 15O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation resampling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two “parallel” networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest; and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.