Corticofugal influences on thalamic neurons during nociceptive transmission in awake rats

Pain is a multidimensional phenomenon and processed in a neural network. The supraspinal, brain mechanisms are increasingly recognized in playing a major role in the representation and modulation of pain. The aim of the current study is to investigate the functional interactions between cortex and thalamus during nociceptive processing, by observing the pain-related information flow and neuronal correlations within thalamo-cortical pathways. Pain-evoked, single-neuron activity was recorded in awake Sprague-Dawley rats with a Magnet system. Eight-wire microarrays were implanted into four different brain regions, i.e., the primary somatosensory (SI) and anterior cingulate cortex (ACC), as well as ventral posterior (VP) and medial dorsal thalamus (MD). Noxious radiant heat was delivered to the rat hind paws on the side contralateral to the recording regions. A large number of responsive neurons were recorded in the four brain areas. Directed coherence analysis revealed that the amount of information flow was significantly increased from SI cortex to VP thalamus following noxious stimuli, suggesting that SI cortex has descending influence on thalamic neurons during pain processing. Moreover, more correlated neuronal activities indicated by crosscorrelation histograms were found between cortical and thalamic neurons, with cortical neurons firing ahead of thalamic units. On basis of the above findings, we propose that nociceptive responses are modulated by corticothalamic feedback during nociceptive transmission, which may be tight in the lateral pathway, while loose in the medial pathway.     

Projections of thalamic gustatory and lingual areas in the monkey, Macaca fascicularis

The efferent projections of the parvicellular division of the ventroposteromedial nucleus of the thalamus (VMPpc; thalamic taste area) were traced to cortex in Macaca fascicularis by using tritiated amino acid autoradiography. Labeled fascicles could be traced from VPMpc to two discrete regions of cortex. The primary efferent projection was located on ipsilateral insular-opercular cortex adjacent to the superior limiting sulcus and extended as far rostrally as the posterior lateral orbitofrontal cortex. An additional projection was located within primary somatosensory (SI) cortex subjacent to the anterior subcentral sulcus. Following autoradiographic injections in VPM, the trigeminal somatosensory relay, a dense terminal plexus was labeled on SI cortex of both pre- and postcentral gyri, but not within insular-opercular cortex. The autoradiographic data were verified by injecting each cortical projection area with horseradish peroxidase (HRP) and observing the pattern of retrogradely labeled somata within the thalamus. Injections in the precentral gyrus near the anterior subcentral sulcus retrogradely labeled neurons within VPMpc, whereas injections further caudally near the floor of the central sulcus labeled neurons within VPM. Injections of HRP within opercular, insular, or posterior lateral orbitofrontal cortex retrogradely labeled neurons within VPMpc.     

Dynamic neuronal responses in cortical and thalamic areas during different phases of formalin test in rats

Although formalin-induced activity in primary afferent fibers and spinal dorsal horn is well described, the forebrain neural basis underlying each phase of behavior in formalin test has not yet been clarified. The present study was designed to investigate the cortical and thalamic neuronal responses and interactions among forebrain areas during different phases after subcutaneous injection of formalin. Formalin-induced neuronal activities were simultaneously recorded from primary somatosensory cortex (SI), anterior cingulate cortex (ACC) and medial dorsal (MD) and ventral posterior (VP) thalamus during different phases (i.e., first phase, interphase, second phase and third recovery phase starting from 70 min after injection) of formalin test, using a multi-channel, single-unit recording technique. Our results showed that, (i) unlike the responses in primary afferent fibers and spinal dorsal horn, many forebrain neurons displayed monophasic excitatory responses in the first hour after formalin injection, except a small portion of neurons which exhibited biphasic responses; (ii) the response patterns of many cortical and thalamic neurons changed from excitatory to inhibitory at the end of the second phase; (iii) the direction of information flow also changed dramatically, i.e., from cortex to thalamus and from the medial to the lateral pathway in the first hour, but reversed in phase 3. These results indicate that the changes of activity pattern in forebrain networks may underlie the emerging and subsiding of central sensitization-induced pain behavior in the second phase of formalin test.     

Hypothermia-induced changes of afferent sensory transmission to the VPM thalamus of rats and hamsters

Effects of hypothermia on the afferent somatosensory transmission to the ventroposteromedial (VPM) thalamus were determined in anesthetized rats and hamsters. Hamsters showed a gradual suppression of afferent sensory transmission during cooling (to 18 degrees C) and disinhibition during subsequent warming of body temperature (Tb). However, rats exhibited steep inhibition from Tb 26 degrees C to complete absence of sensory transmission at Tb 20 degrees C and abrupt disinhibition during subsequent warming. Species difference at thalamic level was quite similar to our previous results in the primary somatosensory (SI) cortex, suggesting that changes of sensory transmission observed in the SI cortex may have already occurred at thalamic level. Differences between the cortex and the thalamus were observed only during deep hypothermia in rat and during the final period of warming in hamster. Conduction latencies of thalamocortical system of both species were not influenced during Tb lowering until 24 degrees C (equivalent to brain temperature 25-26 degrees C). These results suggest inherently different adaptability to hypothermia in processing somatosensory information between hibernator and non-hibernator, but similar sustainability of sensory functions of the thalamocortical system during hypothermia in both species.     

Effects of pentobarbital anesthesia on nociceptive processing in the medial and lateral pain pathways in rats

Objective

To investigate the effects of pentobarbital anesthesia on nociceptive processing in the medial and lateral pain pathways.

Methods

Laser stimulation was employed to evoke nociceptive responses in rats under awake or anesthetic conditions. Pain-related neuronal activities were simultaneously recorded from the primary somatosensory cortex (SI), ventral posterolateral thalamus (VPL), anterior cingulate cortex (ACC), and medial dorsal thalamus (MD) with 4 eight-wire microelectrode arrays.

Results

Compared with the awake state, pentobarbital anesthesia significantly suppressed the neural activities induced by noxious laser stimulation. Meanwhile, the pain-evoked changes in the neuronal correlations between cortex and thalamus were suppressed in both medial and lateral pain pathways. In addition, the spontaneous firing rates in all the 4 areas were altered (including inhibition and excitation) under the condition of anesthesia.

Conclusion

The nociceptive processing in the brain can be dramatically changed by anesthesia, which indicates that there are considerable differences in the brain activities between awake and anesthetized states. It is better to employ awake animals for recording neural activity when investigating the sensory coding mechanisms, especially pain coding, in order to obtain data that precisely reflect the physiological state.     

Calbindin and parvalbumin cells in monkey VPL thalamic nucleus: distribution, laminar cortical projections, and relations to spinothalamic terminations.

The ventral posterior lateral nucleus (VPL) of the monkey thalamus was investigated by histochemical staining for cytochrome oxidase (CO) activity and by immunocytochemical staining for the calcium-binding proteins parvalbumin and 28 kDa calbindin. Anterograde and retrograde tracing experiments were used to correlate patterns of differential distribution of CO activity and of parvalbumin and calbindin cells with the terminations of spinothalamic tract fibers and with the types of cells projecting differentially to superficial and deeper layers of primary somatosensory cortex (SI). VPL is composed of CO-rich and CO-weak compartments. Cells are generally smaller in the CO-weak compartment. Parvalbumin-immunoreactive cells and parvalbumin-immunoreactive medial lemniscal fiber terminations are confined to the CO-rich compartment. Calbindin-immunoreactive cells are found in both the CO-rich and CO-weak compartments. The CO-weak compartment, containing only calbindin cells, forms isolated zones throughout VPL and expands as a cap covering the posterior surface of the ventral posterior medial nucleus (VPM). Spinothalamic tract terminations tend to be concentrated in the CO-weak compartment, especially in the posterior cap. Other CO-weak, parvalbumin-negative, calbindin-positive nuclei, including the posterior, ventral posterior inferior, and anterior pulvinar and the small-celled matrix of VPM are also associated with concentrations of spinothalamic and caudal trigeminothalamic terminations. Parvalbumin cells are consistently larger than calbindin cells and are retrogradely labeled only after injections of tracers in middle and deep layers of SI. The smaller calbindin cells are the only cells retrogradely labeled after placement of retrograde tracers that primarily involve layer I of SI. The compartmental organization of VPL is similar to but less rigid than that previously reported in VPM. VPL and VPM relay cells projecting to different layers of SI cortex can be distinguished by differential immunoreactivity for the two calcium-binding proteins. The small-celled, CO-weak, calbindin-positive zones of VPL and VPM appear to form part of a wider system of smaller thalamic neurons unconstrained by traditional nuclear boundaries that are preferentially the targets of spinothalamic and caudal trigeminal inputs, and that may have preferential access to layer I of SI.     

Experience-induced plasticity of thalamocortical axons in both juveniles and adults

We examined the effect of sensory deprivation on thalamocortical (TC) projections to the rat primary somatosensory cortex at different postnatal ages ranging from P0 to P96. Rats had their whiskers clipped off with one or two vibrissae spared. TC axons innervating barrel cortex were specifically labeled by injecting virus expressing fluorescent proteins into the corresponding primary (VPM) and/or secondary (POm) thalamic nuclei. The density of VPM axons in deprived columns was ≈34% lower relative to spared columns with a concomitant decrease in bouton density, suggesting a deprivation-induced retraction of VPM axons. Axonal changes were reversible upon regrowth of the clipped whiskers and independent of age at deprivation, indicating the absence of a critical period for anatomical plasticity. The POm projection was not obviously altered by sensory deprivation. We suggest that retraction and regrowth of TC axons substantially contribute to long-term deprivation-dependent functional plasticity.     

Origin and distribution of noradrenergic innervation in the habenula: A neurochemical study

Retrograde axonal transport of fluorescent dyes was used to demonstrate collateral projections from neurons of the pontine taste area (PTA) to gustatory-responsive areas of the posterior ventromedial thalamic nucleus (VPM), and to the gustatory neocortex (GN) of the rat. Dual-labeled PTA neurons were reliably observed following application of two different fluorescent dyes to the GN and to VPM thalamus. Dye injections into the GN and into thalamic regions surrounding the VPM nucleus, the bed nucleus of stria terminalis or the infralimbic neocortex, did not result in dual-labeled cells within the PTA. This finding suggests that gustatory information may be relayed simultaneously and specifically to VPM thalamus and to the GN via collateral axons of PTA neurons.     

Axon collaterals of pontine taste area neurons project to the posterior ventromedial thalamic nucleus and to the gustatory neocortex

Retrograde axonal transport of fluorescent dyes was used to demonstrate collateral projections from neurons of the pontine taste area (PTA) to gustatory-responsive areas of the posterior ventromedial thalamic nucleus (VPM), and to the gustatory neocortex (GN) of the rat. Dual-labeled PTA neurons were reliably observed following application of two different fluorescent dyes to the GN and to VPM thalamus. Dye injections into the GN and into thalamic regions surrounding the VPM nucleus, the bed nucleus of stria terminalis or the infralimbic neocortex, did not result in dual-labeled cells within the PTA. This finding suggests that gustatory information may be relayed simultaneously and specifically to VPM thalamus and to the GN via collateral axons of PTA neurons.     

Corticothalamic neurons and thalamocortical terminal fields: an investigation in rat using horseradish peroxidase and autoradiography.

Subsequent to thalamic injections in rats of horseradish peroxidase (HRP) alone or HRP and [3H]leucine in combination, the cells of origin of the corticothalamic projections and the terminal fields of the thalamocortical projections were identified. HRP-labeled corticothalamic neurons were uniformly found in layers V and VI. They were medium to small in size and always pyramidal in shape with the larger neurons being found in layer V. On the other hand, 3 different patterns for the distribution of thalamocortical terminal fields were observed. The autoradiographic material indicated that in prefrontal cortex the bulk of thalamocortical fibers terminate in layer III while in motor cortex they terminate primarily in layer V. A third pattern was shared by temporal, occipital and parietal cortex where the bulk of thalamocortical fibers terminate preferentially in layer IV. The data derived from the rats which had received thalamic injections of HRP and [3H]leucine in combination indicated that the connections between cortex and thalamus are in general reciprocal. These results are discussed with regard to earlier studies using classical or more recently developed neuroanatomical methods.     

Dual pathways for thermal afferents from the cat''s tongue

In the lightly anesthetized cat, pathways transmitting cold afferents from the tongue to the first somatosensory cortex (SI) and to the preoptic/anterior hypothalamic (PO/AH) area were analyzed electrophysiologically. Thalamic cold-sensitive neurons that are responsive to cold stimulation of the tongue were found in the dorsomedial and caudal part of the medial ventroposterior nucleus (VPM). These thalamic neurons received synaptic inputs from the neurons in the subnucleus caudalis of the spinal trigeminal nuclei. Many of the neurons in the SI activated by stimulation of the cold-sensitive area in the VPM responded to cold stimulation of the tongue. Blocking the neural activity around the thalamic cold-sensitive area by injecting a solution of xylocaine resulted in a lack of responsiveness to cold stimulation of the tongue in the cortical cold-sensitive neurons. There were neurons in the PO/AH area responsive to such cold stimulation. These neurons were activated by electrical stimulation of the cold-sensitive area in the subnucleus caudalis, but not by stimulation of the cold-sensitive area in the VPM. These results suggested the possible existence of dual pathways for cold afferents from the tongue. One is the pathway to the SI through the VPM and the other to the PO/AH area. The signal transmission speed of the former was markedly faster than that of the latter.     

Adult rat motor cortex connections to thalamus following neonatal and juvenile frontal cortical lesions: WGA-HRP and amino acid studies

Frontal cortex was removed in 1- and 30-day-old rats. When both groups reached 90 days of age, the forelimb motor/sensory cortex in the unlesioned hemisphere was injected with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or tritiated leucine. Thalamic neurons were retrogradely labeled only ipsilateral to the WGA-HRP injection site in both neonatally and juvenile-lesioned subjects. Ventrolateral (VL), ventromedial (VM), centromedial (CM), centrolateral (CL), parafascicular (PF), posteromedial (POm), and posterior (PO) thalamic nuclei were labeled. This and the demonstration of only ipsilateral thalamocortical connections at birth helped explain the marked thalamic atrophy which developed ipsilateral to neonatal frontal cortex lesions. Death of thalamic neurons after neonatal removal of their normal cortical target could be due to their failure to sprout into the opposite cortex because that cortex was already innervated by the opposite thalamus at birth. Leucine motor/sensory cortex injections in both neonatally and juvenile-lesioned subjects labeled the ipsilateral VL, VM, CM, CL, PF, POm, and PO thalamic nuclei; contralateral CM, CL, and PF thalamic nuclei; ipsilateral medial, ventral, and lateral pontine nuclei; and parts of the contralateral pontine nuclei. The ipsilateral connections were always more robust than the contralateral connections. The contralateral corticothalamic and corticopontine projections, however, were much more numerous and widespread in neonatally compared to juvenile-lesioned subjects. The greater sparing of some motor functions said to occur in neonatal compared to adult motor cortex-lesioned subjects could be due to the plasticity of corticothalamic, corticopontine, and other corticofugal pathways, but not to the plasticity of thalamocortical pathways.     

Common fur and mystacial vibrissae parallel sensory pathways: 14 C 2-deoxyglucose and WGA-HRP studies in the rat

Stimulation of mystacial vibrissae in rows A,B, and C increased (14C) 2-deoxyglucose (2DG) uptake in spinal trigeminal nucleus pars caudalis (Sp5c) mostly in ventral portions of laminae III-IV with less activation of II and V. Stimulation of common fur above the whiskers mainly activated lamina II, with less activation in deeper layers. The patterns of activation were compatible with an inverted head, onion skin Sp5c somatotopy. Wheatgerm Agglutinin-Horseradish Peroxidase (WGA-HRP) injections into common fur between mystacial vibrissae rows A-B and B-C led to anterograde transganglionic labeling only of Sp5c, mainly of lamina II with less label in layer V, and very sparse label in III and IV. WGA-HRP skin injections appear to primarily label small fibers, which along with larger fibers, were metabolically activated during common fur stimulation. Mystacial vibrissae stimulation increased 2DG uptake in ventral ipsilateral spinal trigeminal nuclei pars interpolaris (Sp5i) and oralis (Sp5o) and principal trigeminal sensory nucleus (Pr5). Common fur stimulation above the whiskers slightly increased 2DG uptake in ventral Sp5i, Sp5o, and possibly Pr5. The most dorsal aspect of the ventroposteromedial (VPM) nucleus of thalamus was activated contralateral to whisker stimulation. Stimulation of the common fur dorsal to the whiskers activated a region of dorsal VPM caudal to the VPM region activated during whisker stimulation. This is consistent with previous data showing that ventral whiskers and portions of the face are represented rostrally in VPM, and more dorsal whiskers and dorsal portions of the face are represented progressively more caudally in VPM. Mystacial vibrissae stimulation activated the contralateral primary sensory SI barrelfield cortex and a separate region in the second somatosensory SII cortex. Common fur stimulation above the whiskers activated a cortical region between the SI and SII whisker activated regions of cortex. It is proposed that this region represented the combined SI and SII common fur regions of somatosensory neocortex. Both whisker and common fur stimulation activated all layers of cortex, with layer IV being most activated followed by II-III, V, and VI. These data indicate that sensory input from the mystacial vibrissae in the adult rat is processed in brainstem, thalamic, and cortical pathways which are predominantly parallel to those which process information from the neighboring common fur sensory receptors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Diencephalic projections from the superficial and deep laminae of the medullary dorsal horn in the rat.

An important function of the medullary dorsal horn (MDH) is the relay of nociceptive information from the face and mouth to higher centers of the central nervous system. We studied the central projection pattern of axons arising from the MDH by examining the axonal transport of Phaseolus vulgaris-leucoagglutinin (PHA-L). Labeled axon and axon terminal distributions arising from the MDH were analyzed at the light microscopic level. After large injections of PHA-L into both superficial and deep laminae of the MDH in the rat, labeled axons were observed in the nucleus submedius of the thalamus (SUB), ventroposterior thalamic nucleus medialis (VPM), ventroposterior thalamic nucleus parvicellularis (VPPC), posterior thalamic nuclei (PO), zona incerta (ZI), lateral hypothalamic nucleus (LH), and posterior hypothalamic nucleus (PH). Restriction of PHA-L into only the superficial laminae resulted in heavy axon and varicosity labeling in the SUB, VPM, PO, and VPPC and light labeling in LH. In contrast, after injections into deep laminae, labeled axons were mainly distributed in ZI and PH; some were also in VPM and LH, and fewer still in PO and SUB. Varicosities in VPM, SUB, and PO were significantly larger than those in VPPC, ZI, LH, and PH. Varicosity density was highest in SUB and lowest in the VPPC. We concluded that there are two distinct nociceptive pathways, one originating from the superficial MDH and terminating primarily in the dorsal diencephalon and the second originating from deep laminae of the MDH and terminating primarily in the ventral diencephalon. We propose that in the rat, input from the deeper laminae is primarily involved in the motivational-affective component of pain, whereas input from the superficial MDH is related to both the sensory-discriminative and motivational-affective component of pain.     

Volumetric abnormalities in connectivity-based subregions of the thalamus in patients with chronic schizophrenia

OBJECTIVE: The thalamus, which consists of multiple subnuclei, has been of particular interest in the study of schizophrenia. This study aimed to identify abnormalities in the connectivity-based subregions of the thalamus in patients with schizophrenia. METHODS: Thalamic volume was measured by a manual tracing on superimposed images of T1-weighted and diffusion tensor images in 30 patients with schizophrenia and 22 normal volunteers. Cortical regional volumes automatically measured by a surface-based approach and thalamic subregional volumes measured by a connectivity-based technique were compared between the two groups and their correlations between the connected regions were calculated in each group. RESULTS: Volume reduction was observed in the bilateral orbitofrontal cortices and the left cingulate gyrus on the cortical side, whereas in subregions connected to the right orbitofrontal cortex and bilateral parietal cortices on the thalamic side. Significant volumetric correlations were identified between the right dorsal prefrontal cortex and its related thalamic subregion and between the left parietal cortex and its related thalamic subregion only in the normal group. CONCLUSIONS: Our results suggest that patients with schizophrenia have a structural deficit in the corticothalamic systems, especially in the orbitofrontal-thalamic system. Our findings may present evidence of corticothalamic connection problems in schizophrenia.     

Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis

Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.     

Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory

Four main theories on the pathophysiology of generalized absence seizures have been proposed. The "centrencephalic" theory, proposed in 1954, suggested that discharges originate from a deep-seated diffusely projecting subcortical pacemaker in the midline thalamus. This concept was refined in 1991 with the "thalamic clock" theory, implying that the reticular thalamic nucleus contains the pacemaker cells for the thalamic clock, imposing its rhythm to the cortex. According to other investigators, however, the cortex seems to play a leading role. They suggested that spike-wave discharges have a focal onset in the cortex and are generalized through a rapid propagation. In the "corticoreticular" theory, postulated in 1968, spike-wave discharges are linked to the thalamocortical mechanisms that generate spindles. Rhythmic spindle oscillations generated in the thalamus are transformed into spike-wave discharges when the cortex is hyperexcitable. A 2002 study confirmed in epileptic rats that a functionally intact thalamocortical network is required for the generation of spike-wave discharges. The corticothalamic interrelationships were investigated by means of nonlinear association signal analyses of multiple spike-wave discharges. This showed a consistent focus within the perioral region of the somatosensory cortex. From this focus, seizure activity generalizes rapidly over the cortex. During the first cycles of the seizure the cortex drives the thalamus, while thereafter cortex and thalamus drive each other, thus amplifying and maintaining the rhythmic discharge. In this way the "cortical focus" theory for generalized absence epilepsy bridges cortical and thalamic theories.     

Functional imaging of brain responses to pain. A review and meta-analysis (2000).

Brain responses to pain, assessed through positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are reviewed. Functional activation of brain regions are thought to be reflected by increases in the regional cerebral blood flow (rCBF) in PET studies, and in the blood oxygen level dependent (BOLD) signal in fMRI. rCBF increases to noxious stimuli are almost constantly observed in second somatic (SII) and insular regions, and in the anterior cingulate cortex (ACC), and with slightly less consistency in the contralateral thalamus and the primary somatic area (SI). Activation of the lateral thalamus, SI, SII and insula are thought to be related to the sensory-discriminative aspects of pain processing. SI is activated in roughly half of the studies, and the probability of obtaining SI activation appears related to the total amount of body surface stimulated (spatial summation) and probably also by temporal summation and attention to the stimulus. In a number of studies, the thalamic response was bilateral, probably reflecting generalised arousal in reaction to pain. ACC does not seem to be involved in coding stimulus intensity or location but appears to participate in both the affective and attentional concomitants of pain sensation, as well as in response selection. ACC subdivisions activated by painful stimuli partially overlap those activated in orienting and target detection tasks, but are distinct from those activated in tests involving sustained attention (Stroop, etc.). In addition to ACC, increased blood flow in the posterior parietal and prefrontal cortices is thought to reflect attentional and memory networks activated by noxious stimulation. Less noted but frequent activation concerns motor-related areas such as the striatum, cerebellum and supplementary motor area, as well as regions involved in pain control such as the periaqueductal grey. In patients, chronic spontaneous pain is associated with decreased resting rCBF in contralateral thalamus, which may be reverted by analgesic procedures. Abnormal pain evoked by innocuous stimuli (allodynia) has been associated with amplification of the thalamic, insular and SII responses, concomitant to a paradoxical CBF decrease in ACC. It is argued that imaging studies of allodynia should be encouraged in order to understand central reorganisations leading to abnormal cortical pain processing. A number of brain areas activated by acute pain, particularly the thalamus and anterior cingulate, also show increases in rCBF during analgesic procedures. Taken together, these data suggest that hemodynamic responses to pain reflect simultaneously the sensory, cognitive and affective dimensions of pain, and that the same structure may both respond to pain and participate in pain control. The precise biochemical nature of these mechanisms remains to be investigated.     

Transition from spindles to generalized spike and wave discharges in the cat: Simultaneous single-cell recordings in cortex and thalamus

The relationships between the activity of the cortex and that of a “specific” (n. lateralis posterior, LP) and an intralaminar thalamic nucleus (n. centralis medialis, NCM) were studied in the cat during the transition from spontaneous spindles to generalized spike and wave (SW) discharge following i.m. penicillin injection. The EEG and extracellular single-unit activity were recorded in cortex and thalamus during the spindle stage and at different intervals after penicillin until well developed SW discharges were present. Computer-generated EEG averages and histograms of single-unit activity were triggered by either peaks of cortical or thalamic EEG transients or by cortical or thalamic action potentials. In agreement with previous observations, cortical neurons increasingly fired during the spindle wave as it was transformed into the “spike” of the SW complex, while a period of neuronal silence gradually developed as the “wave” of the SW complex emerged. Similar changes developed in the thalamus, particularly in LP, either concurrently with or more often after the onset of the changes in the cortex. Most neurons in NCM, continued to fire randomly even after well developed SWs and rhythmic neuronal discharges had developed in cortex and LP. Only $\text{4}\text{11}$ NCM neurons did ultimately exhibit a rhythmic firing pattern similar to that seen in the cortex and LP. The correlation between cortical and thalamic unit activity was low during spindles, but gradually increased during the development of SW discharges. These data confirm that the cortex is the leading element in the transition from spindles to SWs. Increasingly, in the course of this transition, cortical and thalamic neuronal firing becomes more intimately phase-locked. This mutual interrelationship appears to be more pronounced between cortex and “specific” than intralaminar thalamic nuclei.