Nina Forss

Altered central sensorimotor processing in patients with complex regional pain syndrome

&NA; Alterations in tactile sensitivity are common in patients with chronic pain. Recent brain imaging studies have indicated that brain areas activated by acute experimental pain partly overlap with areas processing innocuous tactile stimuli. However, the possible effect of chronic pain on central tactile processing has remained unclear. We have examined, both clinically and with whole‐head magnetoencephalography, six patients suffering from complex regional pain syndrome (CRPS) of the upper limb. The cortical somatosensory responses were elicited by tactile stimuli applied to the fingertips and the reactivity of spontaneous brain oscillations was monitored as well. Tactile stimulation of the index finger elicited an initial activation at 65 ms in the contralateral SI cortex, followed by activation of the ipsi‐ and contralateral SII cortices at about 130 ms. The SI responses were 25–55% stronger to stimulation of the painful than the healthy side. The distance between SI representations of thumb and little finger was significantly shorter in the hemisphere contralateral than ipsilateral to the painful upper limb. In addition, reactivity of the 20‐Hz motor cortex rhythm to tactile stimuli was altered in the CRPS patients, suggesting modified inhibition of the motor cortex. These results imply that chronic pain may alter central tactile and motor processing.

Activation of a distributed somatosensory cortical network in the human brain. A dipole modelling study of magnetic fields evoked by median nerve stimulation. Part I: location and activation timing of SEF sources

Cortical areas responsive to somatosensory inputs were assessed by recording somatosensory evoked magnetic fields (SEF) to electrical stimulation of the left median nerve at wrist, using a 122-SQUID neuromagnetometer in various conditions of stimulus rate, attentional demand and detection task. Source modelling combined with magnetic resonance imaging (MRI) allowed localisation of six SEF sources on the outer aspect of the hemispheres located respectively: (1) in the posterior bank of the rolandic fissure (area SI), the upper bank of the sylvian fissure (parietal opercular area SII) and the banks of the intraparietal fissure contralateral to stimulation, (2) in the SII area ipsilateral to stimulation and (3) in the mid-frontal or inferior frontal gyri on both sides. All source areas were found to be simultaneously active at 70-140 ms after the stimulus, the SI source was the only one active already at 20-60 ms. The observed activation timing suggests that somatosensory input from SI is processed to higher-order areas through serial feedforward projections. However the long-lasting activations of all sources and their overlap in time is also compatible with a top-down control mediated via backward projections.

Activation of the human posterior parietal cortex by median nerve stimulation

We recorded somatosensory evoked magnetic fields from ten healthy, right-handed subjects with a 122-channel whole-scalp SQUID magnetometer. The stimuli, exceeding the motor threshold, were delivered alternately to the left and right median nerves at the wrists, with interstimulus intervals of 1, 3, and 5 s. The first responses, peaking around 20 and 35 ms, were explained by activation of the contralateral primary somatosensory cortex (SI) hand area. All subjects showed additional deflections which peaked after 85 ms; the source locations agreed with the sites of the secondary somatosensory cortices (SII) in both hemispheres. The SII responses were typically stronger in the left than the right hemisphere. All subjects had an additional source, not previously reported in human evoked response data, in the contralateral parietal cortex. This source was posterior and medial to the SI hand area, and evidently in the wall of the postcentral sulcus. It was most active at 70–110 ms.

Bilateral activation of the human somatomotor cortex by distal hand movements

We recorded cortical magnetic signals, simultaneously over the whole scalp, from 6 healthy subjects during 3 motor tasks to track the varying proportion of contra- vs. ipsilateral activation. The subjects performed self-paced index finger flexions, simultaneous flexion of 4 fingers, and a sequence of rapid digit movements in different sessions. Index finger and 4-finger movements were associated with phasic bilateral dampening of spontaneous 10 and 20 Hz rhythms along the central sulcus, starting approximately 1 sec before the movement in the contralateral hemisphere. A rebound occurred within 1 sec after the index finger and 4-finger flexions; the rapid finger movements resulted in a persistent blocking of the rhythms. Averaging with respect to movement onset showed a slow bilateral frontal readiness field starting about 0.5 sec prior to motion onset. It was followed, within 200 msec after movement onset, by phasic movement-evoked fields (MEFs) which were bilateral during the tasks involving several fingers. The contra- vs. ipsilateral MEF amplitude ratio C/I decreased from 4.0 during index finger movements to 0.6 during rapid finger flexions, reflecting the enhanced activation of the ipsilateral primary somatomotor cortex with increasing complexity of movement.

Activation of a distributed somatosensory cortical network in the human brain. A dipole modelling study of magnetic fields evoked by median nerve stimulation: Part II: effects of stimulus rate, attention and stimulus detection

In this study we used a repeated measures design and univariate analysis of variance to study the respective effects of ISI, spatial attention and stimulus detection on the strengths of the sources previously identified by modelling SEFs during the 200 ms following mentally counted left median nerve stimuli delivered at long and random ISIs (Part I). We compared the SEF source strengths in response to frequent and rare stimuli, both in detection and ignoring conditions. This permitted us to establish a hierarchy in the effects of ISI, attention and stimulus detection on the activation of the cortical network of SEF sources distributed in SI and posterior parietal cortex contralateral to stimulation, and in the parietal operculum (SII) and premotor frontal cortex of both hemispheres. In all experimental conditions the SI and parietal opercular sources were the most active. All sources were more active in response to stimuli delivered at long and random ISIs and the frontal sources were activated only in this condition of stimulation. Driving the subjects attention toward the side stimulated had no detectable effect on the activity of SEF sources at short ISI. At long ISIs mental counting of the stimuli increased the responses of all sources except SI. These results suggest that activation of frontal sources during mental counting could reflect a working memory process, and that of posterior parietal sources a spatial attention effect detectable only at long ISIs.

Symptomatic intracranial hemorrhage after stroke thrombolysis: The SEDAN Score

A study was undertaken to develop a score for assessing risk for symptomatic intracranial hemorrhage (sICH) in ischemic stroke patients treated with intravenous (IV) thrombolysis.

Comparison of somatosensory evoked fields to airpuff and electric stimuli

We recorded somatosensory evoked magnetic fields (SEFs) from 6 healthy subjects with a 122-channel whole-scalp SQUID gradiometer. In separate experiments, airpuff stimuli were delivered to the dorsum of the proximal phalanx of the middle finger, and electric stimuli were delivered to the median nerve at the wrist; the interstimulus interval was 3 sec and left and right hands were stimulated in subsequent sessions. Airpuffs evoked clear and reproducible responses in all subjects. First responses were recorded over the SI cortex. All subjects showed SII responses both to contra- and ipsilateral airpuffs. The posterior parietal source, identified previously to electric stimulation, was activated also by airpuffs, but only in the right hemisphere. The earliest responses from SI were smaller in amplitude and longer in latency to airpuffs than to electric stimuli; the long-latency responses arising from the other somatosensory areas did not differ significantly.

Aberrant temporal and spatial brain activity during rest in patients with chronic pain

In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective pain-processing areas in patients suffering from chronic pain. The accentuated 0.12- to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system.

Magnetoencephalography in neurosurgery

OBJECTIVE:To present applications of magnetoencephalography (MEG) in studies of neurosurgical patients. METHODS:MEG maps magnetic fields generated by electric currents in the brain, and allows the localization of brain areas producing evoked sensory responses and spontaneous electromagnetic activity. The identified sources can be integrated with other imaging modalities, e.g., with magnetic resonance imaging scans of individual patients with brain tumors or intractable epilepsy, or with other types of brain imaging data. RESULTS:MEG measurements using modern whole-scalp instruments assist in tailoring individual therapies for neurosurgical patients by producing maps of functionally irretrievable cortical areas and by identifying cortical sources of interictal and ictal epileptiform activity. The excellent time resolution of MEG enables tracking of complex spaciotemporal source patterns, helping, for example, with the separation of the epileptic pacemaker from propagated activity. The combination of noninvasive mapping of subcortical pathways by magnetic resonance imaging diffusion tensor imaging with MEG source localization will, in the near future, provide even more accurate navigational tools for preoperative planning. Other possible future applications of MEG include the noninvasive estimation of language lateralization and the follow-up of brain plasticity elicited by central or peripheral neural lesions or during the treatment of chronic pain. CONCLUSION:MEG is a mature technique suitable for producing preoperative “road maps” of eloquent cortical areas and for localizing epileptiform activity.

Modulation of motor-cortex oscillatory activity by painful Aδ- and C-fiber stimuli

Spontaneous approximately 20-Hz oscillations, arising predominantly from the primary motor cortex (MI), are readily observed by magnetoencephalography (MEG). Prior studies have indicated that the level of the approximately 20-Hz rhythm reflects the functional state of the MI cortex: increased 20-Hz level is associated with increased inhibition and suppression of the rhythm with excitation of MI. Close interaction is suggested between pain and the motor system by the association of chronic pain with motor dysfunction and by the alleviation of pain by motor-cortex stimulation. We therefore explored the effect of noxious input on motor-cortex functions by recording MEG signals from nine healthy subjects during selective laser stimulation of Adelta- and C-fibers of the hand. The approximately 20-Hz level was suppressed in the contralateral MI cortex in all nine subjects after painful Adelta- and C-fiber stimuli (P < 0.001). The suppression started 180 +/- 10 ms (mean +/- SEM) after Adelta-fiber stimuli and 820 +/- 30 ms after C-fiber stimuli, and peaked 160-170 ms later. Similar, but about 50% weaker, suppression of the approximately 20-Hz oscillations occurred in seven out of nine subjects in the ipsilateral MI. These results suggest automatic, lateralized, excitation of the MI cortex by noxious Adelta- and C-fiber input.