Evidence against pain specificity in the dorsal posterior insula

The search for a pain centre in the brain has long eluded neuroscientists. Although many regions of the brain have been shown to respond to painful stimuli, all of these regions also respond to other types of salient stimuli. In a recent paper, Segerdahl et al. (Nature Neuroscience, 2015) claims that the dorsal posterior insula (dpIns) is a pain-specific region based on the observation that the magnitude of regional cerebral blood flow (rCBF) fluctuations in the dpIns correlated with the magnitude of evoked pain. However, such a conclusion is, simply, not justified by the experimental evidence provided. Here we discuss three major factors that seriously question this claim

Topodiagnostic implications of hemiataxia: An MRI-based brainstem mapping analysis

The topodiagnostic implications of hemiataxia following lesions of the human brainstem are only incompletely understood. We performed a voxel-based statistical analysis of lesions documented on standardised MRI in 49 prospectively recruited patients with acute hemiataxia due to isolated unilateral brainstem infarction. For statistical analysis individual MRI lesions were normalised and imported in a three-dimensional voxel-based anatomical model of the human brainstem. Statistical analysis revealed hemiataxia to be associated with lesions of three distinct brainstem areas. The strongest correlation referred to ipsilateral rostral and dorsolateral medullary infarcts affecting the inferior cerebellar peduncle, and the dorsal and ventral spinocerebellar tracts. Secondly, lesions of the ventral pontine base resulted in contralateral limb ataxia, especially when ataxia was accompanied by motor hemiparesis. In patients with bilateral hemiataxia, lesions were located in a paramedian region between the upper pons and lower midbrain, involving the decussation of dentato-rubro-thalamic tracts. We conclude that ataxia following brainstem infarction may reflect three different pathophysiological mechanisms. (1) Ipsilateral hemiataxia following dorsolateral medullary infarctions results from a lesion of the dorsal spinocerebellar tract and the inferior cerebellar peduncle conveying afferent information from the ipsilateral arm and leg. (2) Pontine lesions cause contralateral and not bilateral ataxia presumably due to major damage to the descending corticopontine projections and pontine base nuclei, while already crossed pontocerebellar fibres are not completely interrupted. (3) Finally, bilateral ataxia probably reflects a lesion of cerebellar outflow on a central, rostral pontomesencephalic level. © 2007 Elsevier Inc. All rights reserved

Caloric vestibular stimulation modulates nociceptive evoked potentials

Vestibular stimulation has been reported to alleviate central pain. Clinical and physiological studies confirm pervasive interactions between vestibular signals and somatosensory circuits, including nociception. However, the neural mechanisms underlying vestibular-induced analgesia remain unclear, and previous clinical studies cannot rule out explanations based on alternative, non-specific effects such as distraction or placebo. To investigate how vestibular inputs influence nociception, we combined caloric vestibular stimulation (CVS) with psychophysical and electrocortical responses elicited by nociceptive-specific laser stimulation in humans (laser-evoked potentials, LEPs). Cold water CVS applied to the left ear resulted in significantly lower subjective pain intensity for experimental laser pain to the left hand immediately after CVS, relative both to before CVS and to 1 h after CVS. This transient reduction in pain perception was associated with reduced amplitude of all LEP components, including the early N1 wave reflecting the first arrival of nociceptive input to primary somatosensory cortex. We conclude that cold left ear CVS elicits a modulation of both nociceptive processing and pain perception. The analgesic effect induced by CVS could be mediated either by subcortical gating of the ascending nociceptive input, or by direct modulation of the primary somatosensory cortex

Trigeminal neuralgia: Update on reflex and evoked potential studies

[No abstract available

Beyond metaphor: contrasting mechanisms of social and physical pain.

Physical pain can be clearly distinguished from other states of distress. In recent years, however, the notion that social distress is experienced as physically painful has permeated the scientific literature and popular media. This conclusion is based on the overlap of brain regions that respond to nociceptive input and sociocultural distress. Here we challenge the assumption that underlies this conclusion – that physical pain can be easily inferred from a particular pattern of activated brain regions – by showing that patterns of activation commonly presumed to constitute the ‘pain matrix’ are largely unspecific to pain. We then examine recent analytical advances that may improve the specificity of imaging for parsing pain from a broad range of perceptually unique human experiences

EEG signatures of auditory activity correlate with simultaneously recorded fMRI responses in humans

We recorded auditory-evoked potentials (AEPs) during simultaneous, continuous fMRI and identified trial-to-trial correlations between the amplitude of electrophysiological responses, characterised in the time domain and the time–frequency domain, and the hemodynamic BOLD response. Cortical AEPs were recorded from 30 EEG channels within the 3 T MRI scanner with and without the collection of simultaneous BOLD fMRI. Focussing on the Cz (vertex) EEG response, single-trial AEP responses were measured from time-domain waveforms. Furthermore, a novel method was used to characterise the single-trial AEP response within three regions of interest in the time–frequency domain (TF-ROIs). The latency and amplitude values of the N1 and P2 AEP peaks during fMRI scanning were not significantly different from the Control session (p > 0.16). BOLD fMRI responses to the auditory stimulation were observed in bilateral secondary auditory cortices as well as in the right precentral and postcentral gyri, anterior cingulate cortex (ACC) and supplementary motor cortex (SMC). Significant single-trial correlations were observed with a voxel-wise analysis, between (1) the magnitude of the EEG TF-ROI1 (70–800 ms post-stimulus, 1–5 Hz) and the BOLD response in right primary (Heschl's gyrus) and secondary (STG, planum temporale) auditory cortex; and (2) the amplitude of the P2 peak and the BOLD response in left pre- and postcentral gyri, the ACC and SMC. No correlation was observed with single-trial N1 amplitude on a voxel-wise basis. An fMRI-ROI analysis of functionally-identified auditory responsive regions identified further single-trial correlations of BOLD and EEG responses. The TF amplitudes in TF-ROI1 and TF-ROI2 (20–400 ms post-stimulus, 5–15 Hz) were significantly correlated with the BOLD response in all bilateral auditory areas investigated (planum temporale, superior temporal gyrus and Heschl's gyrus). However the N1 and P2 peak amplitudes, occurring at similar latencies did not show a correlation in these regions. N1 and P2 peak amplitude did correlate with the BOLD response in bilateral precentral and postcentral gyri and the SMC. Additionally P2 and TF-ROI1 both correlated with the ACC. TF-ROI3 (400–900 ms post-stimulus, 4–10 Hz) correlations were only observed in the ACC and SMC. Across the group, the subject-mean N1 peak amplitude correlated with the BOLD response amplitude in the primary and secondary auditory cortices bilaterally, as well as the right precentral gyrus and SMC. We confirm that auditory-evoked EEG responses can be recorded during continuous and simultaneous fMRI. We have presented further evidence of an empirical single-trial coupling between the EEG and BOLD fMRI responses, and show that a time–frequency decomposition of EEG signals can yield additional BOLD fMRI correlates, predominantly in auditory cortices, beyond those found using the evoked response amplitude alone

Evidence against pain specificity in the dorsal posterior insula [version 1; referees: 2 approved]

The search for a “pain centre” in the brain has long eluded neuroscientists.  Although many regions of the brain have been shown to respond to painful stimuli, all of these regions also respond to other types of salient stimuli. In a recent paper, Segerdahl et al. (Nature Neuroscience, 2015)  claims that the dorsal posterior insula (dpIns) is a pain-specific region based on the observation that the magnitude of regional cerebral blood flow (rCBF) fluctuations in the dpIns correlated with the magnitude of evoked pain.  However, such a conclusion is, simply, not justified by the experimental evidence provided.  Here we discuss three major factors that seriously question this claim

Coupling of simultaneously acquired electrophysiological and haemodynamic responses during visual stimulation

We investigate the relationship between the temporal variation in the magnitude of occipital visual evoked potentials (VEPs) and of haemodynamic measures of brain activity obtained using both blood oxygenation level dependent (BOLD) and perfusion sensitive (ASL) functional magnetic resonance imaging (fMRI). Volunteers underwent a continuous BOLD fMRI scan and/or a continuous perfusion-sensitive (gradient and spin echo readout) ASL scan, during which 30 second blocks of contrast reversing visual stimuli (at 4 Hz) were interleaved with 30 second blocks of rest (visual fixation). Electroencephalography (EEG) and fMRI were simultaneously recorded and following EEG artefact cleaning, VEPs were averaged across the whole stimulation block (120 reversals, VEP120) and at a finer timescale (15 reversals, VEP15). Both BOLD and ASL time-series were linearly modelled to establish: (1) the mean response to visual stimulation, (2) transient responses at the start and end of each stimulation block, (3) the linear decrease between blocks, (4) the nonlinear between-block variation (covariation with VEP120), (5) the linear decrease within block and (6) the nonlinear variation within block (covariation with VEP15). VEPs demonstrated a significant linear time-dependent reduction in amplitude, both within and between blocks of stimulation. Consistent with the VEPs finding, both BOLD and perfusion measures showed significant linear time-dependent reductions in response amplitude between blocks. In addition, there were significant linear time-dependent within-block reductions in BOLD response as well as between-block variations positively correlating with VEP120 (medial occipital and frontal) and within-block variations positively correlating with VEP15 (occipital and thalamus). Both electrophysiological and haemodynamic (BOLD and ASL) measures of visual activity showed steady habituation through the experiment. Beyond this, the VEP measures were predictive of shorter timescale (3-30 second) localised variations in BOLD response engaging both occipital cortex and other regions such as anterior cingulate and parietal regions, implicating attentional processes in the modulation of the VEP signal

Early-onset hereditary neuropathy with liability to pressure palsy

The clinical onset of hereditary neuropathy with liability to pressure palsy (HNPP) in childhood is rarely reported. On the basis of a 5-year-old affected patient, we reviewed the cases reported in the literature to evaluate the clinical and genetic characteristics of patients with an early onset (< 10 years) of HNPP