The role of human orbitofrontal cortex in value comparison for incommensurable objects.

The human orbitofrontal cortex is strongly implicated in appetitive valuation. Whether its role extends to support comparative valuation necessary to explain probabilistic choice patterns for incommensurable goods is unknown. Using a binary choice paradigm, we derived the subjective values of different bundles of goods, under conditions of both gain and loss. We demonstrate that orbitofrontal activation reflects the difference in subjective value between available options, an effect evident across valuation for both gains and losses. In contrast, activation in dorsal striatum and supplementary motor areas reflects subjects' choice probabilities. These findings indicate that orbitofrontal cortex plays a pivotal role in valuation for incommensurable goods, a critical component process in human decision making.

Anchors, scales and the relative coding of value in the brain.

People are alarmingly susceptible to manipulations that change both their expectations and experience of the value of goods. Recent studies in behavioral economics suggest such variability reflects more than mere caprice. People commonly judge options and prices in relative terms, rather than absolutely, and display strong sensitivity to exemplar and price anchors. We propose that these findings elucidate important principles about reward processing in the brain. In particular, relative valuation may be a natural consequence of adaptive coding of neuronal firing to optimise sensitivity across large ranges of value. Furthermore, the initial apparent arbitrariness of value may reflect the brains' attempts to optimally integrate diverse sources of value-relevant information in the face of perceived uncertainty. Recent findings in neuroscience support both accounts, and implicate regions in the orbitofrontal cortex, striatum, and ventromedial prefrontal cortex in the construction of value.

Opponent appetitive-aversive neural processes underlie predictive learning of pain relief.

Termination of a painful or unpleasant event can be rewarding. However, whether the brain treats relief in a similar way as it treats natural reward is unclear, and the neural processes that underlie its representation as a motivational goal remain poorly understood. We used fMRI (functional magnetic resonance imaging) to investigate how humans learn to generate expectations of pain relief. Using a pavlovian conditioning procedure, we show that subjects experiencing prolonged experimentally induced pain can be conditioned to predict pain relief. This proceeds in a manner consistent with contemporary reward-learning theory (average reward/loss reinforcement learning), reflected by neural activity in the amygdala and midbrain. Furthermore, these reward-like learning signals are mirrored by opposite aversion-like signals in lateral orbitofrontal cortex and anterior cingulate cortex. This dual coding has parallels to 'opponent process' theories in psychology and promotes a formal account of prediction and expectation during pain.

Multiple single unit recording in the cortex of monkeys using independently moveable microelectrodes.

Simultaneous recording from multiple single neurones presents many technical difficulties. However, obtaining such data has many advantages, which make it highly worthwhile to overcome the technical problems. This report describes methods which we have developed to permit recordings in awake behaving monkeys using the 'Eckhorn' 16 electrode microdrive. Structural magnetic resonance images are collected to guide electrode placement. Head fixation is achieved using a specially designed headpiece, modified for the multiple electrode approach, and access to the cortex is provided via a novel recording chamber. Growth of scar tissue over the exposed dura mater is reduced using an anti-mitotic compound. Control of the microdrive is achieved by a computerised system which permits several experimenters to move different electrodes simultaneously, considerably reducing the load on an individual operator. Neurones are identified as pyramidal tract neurones by antidromic stimulation through chronically implanted electrodes; stimulus control is integrated into the computerised system. Finally, analysis of multiple single unit recordings requires accurate methods to correct for non-stationarity in unit firing. A novel technique for such correction is discussed.

Rhythm generation in monkey motor cortex explored using pyramidal tract stimulation.

We investigated whether stimulation of the pyramidal tract (PT) could reset the phase of 15-30 Hz beta oscillations observed in the macaque motor cortex. We recorded local field potentials (LFPs) and multiple single-unit activity from two conscious macaque monkeys performing a precision grip task. EMG activity was also recorded from the second animal. Single PT stimuli were delivered during the hold period of the task, when oscillations in the LFP were most prominent. Stimulus-triggered averaging of the LFP showed a phase-locked oscillatory response to PT stimulation. Frequency domain analysis revealed two components within the response: a 15-30 Hz component, which represented resetting of on-going beta rhythms, and a lower frequency 10 Hz response. Only the higher frequency could be observed in the EMG activity, at stronger stimulus intensities than were required for resetting the cortical rhythm. Stimulation of the PT during movement elicited a greatly reduced oscillatory response. Analysis of single-unit discharge confirmed that PT stimulation was capable of resetting periodic activity in motor cortex. The firing patterns of pyramidal tract neurones (PTNs) and unidentified neurones exhibited successive cycles of suppression and facilitation, time locked to the stimulus. We conclude that PTN activity directly influences the generation of the 15-30 Hz rhythm. These PTNs facilitate EMG activity in upper limb muscles, contributing to corticomuscular coherence at this same frequency. Since the earliest oscillatory effect observed following stimulation was a suppression of firing, we speculate that inhibitory feedback may be the key mechanism generating such oscillations in the motor cortex.

Imaging the femoral cortex: thickness, density and mass from clinical CT.

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm(2)) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex.

Imaging the femoral cortex: Thickness, density and mass from clinical CT

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm 2) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex. © 2012 Elsevier B.V.

Modulation of pain processing in hyperalgesia by cognitive demand.

The relationship between pain and cognitive function is of theoretical and clinical interest, exemplified by observations that attention-demanding activities reduce pain in chronically afflicted patients. Previous studies have concentrated on phasic pain, which bears little correspondence to clinical pain conditions. Indeed, phasic pain is often associated with differential or opposing effects to tonic pain in behavioral, lesion, and pharmacological studies. To address how cognitive engagement interacts with tonic pain, we assessed the influence of an attention-demanding cognitive task on pain-evoked neural responses in an experimental model of chronic pain, the capsaicin-induced heat hyperalgesia model. Using functional magnetic resonance imaging (fMRI), we show that activity in the orbitofrontal and medial prefrontal cortices, insula, and cerebellum correlates with the intensity of tonic pain. This pain-related activity in medial prefrontal cortex and cerebellum was modulated by the demand level of the cognitive task. Our findings highlight a role for these structures in the integration of motivational and cognitive functions associated with a physiological state of injury. Within the limitations of an experimental model of pain, we suggest that the findings are relevant to understanding both the neurobiology and pathophysiology of chronic pain and its amelioration by cognitive strategies.