Niall W. Duncan

Is there a core neural network in empathy? An fMRI based quantitative meta-analysis

Whilst recent neuroimaging studies have identified a series of different brain regions as being involved in empathy, it remains unclear concerning the activation consistence of these brain regions and their specific functional roles. Using MKDA, a whole-brain based quantitative meta-analysis of recent fMRI studies of empathy was performed. This analysis identified the dACC-aMCC-SMA and bilateral anterior insula as being consistently activated in empathy. Hypothesizing that what are here termed affective-perceptual and cognitive-evaluative forms of empathy might be characterized by different activity patterns, the neural activations in these forms of empathy were compared. The dorsal aMCC was demonstrated to be recruited more frequently in the cognitive-evaluative form of empathy, whilst the right anterior insula was found to be involved in the affective-perceptual form of empathy only. The left anterior insula was active in both forms of empathy. It was concluded that the dACC-aMCC-SMA and bilateral insula can be considered as forming a core network in empathy, and that cognitive-evaluative and affective-perceptual empathy can be distinguished at the level of regional activation.

Anterior cingulate activity and the self in disorders of consciousness

Objectives: The aim of this study was to investigate the relationship between medial cortical activation and the presence of self and consciousness in healthy subjects and patients with vegetative state and minimally conscious state using functional magnetic resonance imaging (fMRI). Experiment design: We first conducted two fMRI experiments in healthy subjects to identify brain regions specifically associated with self‐perception through the use of different auditory stimuli that had different grades of self‐relatedness. We then applied these regions as functional localizers to examine the relationship between neural activity changes during self‐relatedness and consciousness level in the patients with disorders of consciousness (DOC). Principal observations: We demonstrated recruitment of various anterior medial cortical regions including the anterior cingulate cortex (ACC) in healthy subjects during auditory perception of self‐related stimuli. We further showed that patients with DOC showed signal changes in the ACC during auditory perception of self‐related stimuli. Finally, it was shown that these signal changes correlate with the level of consciousness in the patients with DOC. Conclusion: The degree of consciousness in patients with DOC was correlated with neural activity in the ACC induced by self‐related stimuli. Our results not only shed light on the pathophysiology of DOC, but may also suggest a useful neural, and thus diagnostic, marker of the dysfunction of consciousness in vegetative patients. Hum Brain Mapp, 2010.

GABA in the insula — a predictor of the neural response to interoceptive awareness

The insula has been identified as a key region involved in interoceptive awareness. Whilst imaging studies have investigated the neural activation patterns in this region involved in intero- and exteroceptive awareness, the underlying biochemical mechanisms still remain unclear. In order to investigate these, a well-established fMRI task targeting interoceptive awareness (heartbeat counting) and exteroceptive awareness (tone counting) was combined with magnetic resonance spectroscopy (MRS). Controlling for physiological noise, neural activity in the insula during intero- and exteroceptive awareness was confirmed in an independent data sample using the same fMRI design. Focussing on MRS values from the left insula and combining them with neural activity during intero- and exteroceptive awareness in the same healthy individuals, we demonstrated that GABA concentration in a region highly involved in interoceptive processing is correlated with neural responses to interoceptive stimuli, as opposed to exteroceptive stimuli. In addition, both GABA and interoceptive signal changes in the insula predicted the degree of depressed affect, as measured by the Beck Hopelessness Scale. On the one hand, the association between GABA concentration and neural activity during interoceptive awareness provides novel insight into the biochemical underpinnings of insula function and interoception. On the other, through the additional association of both GABA and neural activity during interoception with depressed affect, these data also bear potentially important implications for psychiatric disorders like depression and anxiety, where GABAergic deficits, altered insula function and abnormal affect coincide.

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network

Neuropsychiatric syndromes are highly prevalent in Alzheimers disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or “resting‐state” analysis, may help to clarify this issue. Using such approaches, alterations in the default‐mode and salience networks (SNs) have been described in Alzheimers, although their relationship with specific symptoms remains unclear. We therefore carried out resting‐state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimers patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default‐mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy. Hum Brain Mapp 35:1237–1246, 2014.

Dissociation between anterior and posterior cortical regions during self-specificity and familiarity: a combined fMRI-meta-analytic study.

The familiarity to the subject of any potential stimuli presents one of the major difficulties for the investigation of the self; the separation of effects resulting from familiarity from self‐effects being extremely problematic. The aim of this study was thus to investigate the neural distinction between self and familiarity by combining two sets of fMRI data with a meta‐analysis. In the first fMRI experiment, regions responding to self/familiarity were investigated using the subjects own name and names of familiar others. These effects were confirmed and extended in a second fMRI experiment using the subjects own name and a strangers name, as spoken by familiar and unfamiliar voices. Finally, a meta‐analysis of self‐ and familiarity‐related studies was conducted. Neural activity in the anterior brain regions, such as the anterior cingulate (ACC) and anterior insula (AI), was found to be specific for self‐specific stimuli. In contrast, posterior brain regions, such as the posterior cingulate, were activated by familiar stimuli. Finally, the distinction between anterior and posterior regions for self and familiarity was confirmed by meta‐analytic data. This study demonstrates a clear anterior–posterior cortical partition between self‐specificity and familiarity. Hum Brain Mapp, 2012.

Abnormal body perception and neural activity in the insula in depression: An fMRI study of the depressed "material me"

Abstract Objectives. In addition to affective-cognitive symptoms, patients with major depressive disorder (MDD) suffer from somato-vegetative symptoms, suggesting abnormal interoceptive awareness of their “material me”. While recent imaging studies have extensively investigated affective-cognitive symptoms in MDD, the neural correlates of somato-vegetative symptoms and abnormal interoception remain unclear. Since the “material me” has been especially associated with the anterior insula in healthy subjects, we hypothesized abnormalities in this region during interoceptive awareness in MDD. Methods. We therefore investigated behavioural and neural correlates of interoception in healthy and depressed subjects using the Body Perception Questionnaire (BPQ) and a well established heartbeat perception task in fMRI. Results. MDD patients showed significantly higher scores in the BPQ and reduced neural activity during rest periods, particularly in the bilateral anterior insula. In contrast to healthy subjects, BPQ scores no longer correlated with activity during rest periods in the anterior insula. Both BPQ scores and left anterior insula signal changes correlated with depression severity. Conclusions. We demonstrate for the first time abnormal body perception and altered activity in the insula during rest in MDD. Our results suggest that these behavioural and neural abnormalities are closely related to these patients’ somato-vegetative abnormalities and their abnormal “material me”.

Associations of regional GABA and glutamate with intrinsic and extrinsic neural activity in humans—A review of multimodal imaging studies

The integration of multiple imaging modalities is becoming an increasingly well used research strategy for studying the human brain. The neurotransmitters glutamate and GABA particularly lend themselves towards such studies. This is because these transmitters are ubiquitous throughout the cortex, where they are the key constituents of the inhibition/excitation balance, and because they can be easily measured in vivo through magnetic resonance spectroscopy, as well as with select positron emission tomography approaches. How these transmitters underly functional responses measured with techniques such as fMRI and EEG remains unclear though, and was the target of this review. Consistently shown in the literature was a negative correlation between GABA concentrations and stimulus-induced activity within the measured region. Also consistently found was a positive correlation between glutamate concentrations and inter-regional activity relationships, both during tasks and rest. These findings are outlined along with results from populations with mental disorders to give an overview of what brain imaging has suggested to date about the biochemical underpinnings of functional activity in health and disease. We conclude that the combination of functional and biochemical imaging in humans is an increasingly informative approach that does however require a number of key methodological and interpretive issues be addressed before can meet its potential.

A comparison of neural responses to appetitive and aversive stimuli in humans and other mammals.

Distinguishing potentially harmful or beneficial stimuli is necessary for the self-preservation and well-being of all organisms. This assessment requires the ongoing valuation of environmental stimuli. Despite much work on the processing of aversive- and appetitive-related brain signals, it is not clear to what degree these two processes interact across the brain. To help clarify this issue, this report used a cross-species comparative approach in humans (i.e. meta-analysis of imaging data) and other mammals (i.e. targeted review of functional neuroanatomy in rodents and non-human primates). Human meta-analysis results suggest network components that appear selective for appetitive (e.g. ventromedial prefrontal cortex, ventral tegmental area) or aversive (e.g. cingulate/supplementary motor cortex, periaqueductal grey) processing, or that reflect overlapping (e.g. anterior insula, amygdala) or asymmetrical, i.e. apparently lateralized, activity (e.g. orbitofrontal cortex, ventral striatum). However, a closer look at the known value-related mechanisms from the animal literature suggests that all of these macroanatomical regions are involved in the processing of both appetitive and aversive stimuli. Differential spatiotemporal network dynamics may help explain similarities and differences in appetitive- and aversion-related activity.

The brain and its resting state activity—Experimental and methodological implications

Despite all the recent progress in neuroscience, we still do not understand the basic principles according to which the brain functions. This may be due, at least in part, to our lack of knowledge how the brains intrinsic activity, the brains input, impacts stimulus-induced changes in the brain. We here discuss the neuronal, experimental and methodological relevance of the brains resting state activity for future studies. Furthermore, we make several suggestions how to best define and include the brains resting state into our experimental designs. We conclude that experimental consideration of the brains resting state has major implications for setting up experimental designs and methodological strategies. This may also shed new light on some hitherto unresolved questions like the neuroscientific mechanisms underlying consciousness and psychiatric disorders.

Involvement of glutamate in rest-stimulus interaction between perigenual and supragenual anterior cingulate cortex: a combined fMRI-MRS study.

The brain shows a high degree of activity at rest. The significance of this activity has come increasingly into focus. At present, however, the interaction between this activity and stimulus‐induced activity is not well defined. The interaction between a task‐negative (perigenual anterior cingulate cortex, pgACC) and task‐positive (supragenual anterior cingulate cortex, sgACC) region during a simple task was thus investigated using a combination of fMRI and MRS. Negative BOLD responses in the pgACC were found to show a unidirectional effective connectivity with task‐induced positive BOLD responses in the sgACC. This connectivity was shown to be related specifically with glutamate levels in the pgACC. These results demonstrate an interaction between deactivation from resting‐state and resting‐state glutamate levels in a task‐negative region (pgACC), and task‐induced activity in a task‐positive region (sgACC). This provides insight into the neuronal and biochemical mechanisms by means of which the resting state activity of the brain potentially impacts upon subsequent stimulus‐induced activity. Hum Brain Mapp, 2011.