The neuronal correlates of intranasal trigeminal function—an ALE meta-analysis of human functional brain imaging data

Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO₂), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices—a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO₂ stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing.     

Lateralisation of intranasal trigeminal chemosensory event-related potentials.

AIM OF THE STUDY: To determine whether or not chemosensory event-related brain potentials (CSERP) elicited by nociceptive unilateral intranasal (CO2) trigeminal stimulation are lateralized and, if they are, whether this hemispheric lateralization is related to the side of the stimulated nostril. METHODS: Nine healthy right-handed subjects participated to the study. CSERPs were recorded after left or right monorhinal CO2 stimulation. Latency and baseline-to-peak amplitude of each CSERP component were compared across stimulation conditions (left and right nostril), scalp locations (lower-frontal, frontal, mid-temporal, central, posterior-temporal, parietal) and hemispheres (left or right), using a three-factor analysis of variance (ANOVA) for repeated measures. RESULTS: Intranasal trigeminal CO2 stimulation elicited a large N400-P550 complex. This complex was preceded by an earlier N300 component. Whatever the stimulated nostril, N300, N400 and P550 amplitudes were significantly higher on the right as compared to the left hemisphere, at lower-frontal recording sites. The side of chemosensory stimulation (left or right nostril) did not significantly affect CSERP components. CONCLUSIONS: This study showed that in healthy right-handed volunteers with normal olfactory ability, intranasal chemosensory trigeminal stimulation may elicit a series of event-related brain potentials, which all display a significant right-hemisphere predominance, irrespective of the stimulated nostril. The observed lateralization was maximal at lower-frontal recording sites.     

Assessment of olfactory and trigeminal function using chemosensory event-related potentials.

GOALS: To give an overview on the theoretical and practical applications of chemosensory event-related potentials. METHODS: Chemosensory event-related potentials (ERPs) may be elicited by brief and precisely defined odorous stimuli. Based on the principles of air-dilution olfactometry, a stimulator was developed in the late 1970s, which allows stimulation of the olfactory neuroepithelium and the nasal mucosa with no concomitant mechanical stimulation. Chemosensory ERPs were obtained after stimulation of the olfactory nerve (olfactory ERPs) or the trigeminal nerve (somatosensory or trigeminal ERPs). The characteristics of the stimulator for chemosensory research as well as the variables influencing the responses are discussed in this paper. RESULTS: Implementation and normative data from our department are reported with different clinical examples from otorhinolaryngologic clinic. The bulk of the evoked response consists of a large negative component (often referred to as N1), which occurs between 320 and 450 ms after stimulus onset. This component is followed by a large positive component, often referred to as P2, occurring between 530 and 800 ms after stimulus onset. Absence of olfactory ERPs and presence (even with subtle changes) of somatosensory ERPs is a strong indicator of the presence of an olfactory dysfunction. CONCLUSIONS: This review examines and discusses the methods of chemosensory stimulation as well as the electrophysiological correlates elicited by such stimuli. The clinical applications of chemosensory ERPs in neurology and otorhinolaryngology are outlined.     

Odorant differentiated pattern of cerebral activation: comparison of acetone and vanillin

Whether different odorous compounds (odorants) are processed by different cerebral circuits is presently unknown. A first step to address this complicated issue is to investigate how the cerebral regions mediating signals from olfactory (i.e., unimodal) odorants, differ from those mediating the olfactory + trigeminal (i.e., bimodal) odorants. [15O]-H2O-PET scans were conducted in 12 healthy females during three separate conditions: birhinal, passive smelling of: 1) the unimodal odorant vanillin; 2) the bimodal odorant acetone; and 3) odorless air. Significant activations were calculated contrasting vanillin to air, acetone to air, and deactivations, running these contrasts in the opposite direction. Smelling of vanillin activated bilaterally the amygdala and piriform cortex. These regions were only engaged slightly by acetone. Instead, strong activations were found in the anterior and central insula and claustrum, the posterior portion of anterior cingulate, the somatosensory cortex (SI for face), cerebellum, ventral medial (VMPo) and dorsal medial (MDvc) thalamus, the lateral hypothalamus, and pons/medulla. In parallel, the somatosensory (SI, below central representation of face), secondary visual and auditory cortices, as well as the supplementary motor area and the parahippocampal gyri were deactivated. No deactivations were observed with vanillin, although the odor components of acetone and vanillin were rated similarly intense (75 +/- 17 mm vs. 61 +/- 22 mm, NS). The differentiated pattern of cerebral activation during odorant perception seems to be dependent on the signal transducing cranial nerves involved. In contrast to vanillin, which solely activates the olfactory cortex, acetone engages predominantly trigeminal projections from the nasal mucosa. Acetone's limited activation of the olfactory cortex may result from a cross-modal interaction, with inhibition of acetone's odor component by its trigeminal component.     

Chemosensory event-related potentials in relation to side of stimulation, age, sex, and stimulus concentration.

OBJECTIVE: For chemosensory event-related potentials (ERP) significant effects of age and sex have been demonstrated. The aim of the present study was to assess the effects of stimulus concentration, side of stimulation, and sex on the topographical distribution of chemosensory ERP in a large group of subjects stratified for different age groups. In addition, psychophysical measures of both olfactory and trigeminal function should be assessed in greater detail compared to previous work. METHODS: A total of 95 healthy subjects participated in the study. Olfactory functions were tested using the 'Sniffin' Sticks' comprising tests of odor identification, odor discrimination, and odor threshold. Trigeminal sensitivity was assessed on a psychophysical level using a lateralization paradigm. ERP to the olfactory stimulant H2S and the trigeminal irritant CO2 were recorded; stimuli were presented in different concentrations to the left and right nostril. RESULTS: Olfactory thresholds exhibited an age-related increase while the outcome of psychophysical trigeminal tests was not significantly affected by age. In contrast, there was no significant main effect of the factor 'sex' for olfactory tests, while women scored higher than men in the trigeminal task. ERP to olfactory and trigeminal stimuli exhibited a relationship to stimulus concentration, age, and sex with youngest women showing largest amplitudes and shortest latencies. There was no significant main effect of left- or right-sided stimulation on ERP. Measures of olfactory function were found to correlate with parameters of olfactory ERP even when controlling for the subject's age. In addition, correlations between scores in the lateralization task and parameters of the trigeminal ERP were found. CONCLUSIONS: Based on electrophysiological data obtained in a large sample size the present results established an age-related loss of olfactory and trigeminal function, which appears to be almost linear. Further, the present results emphasize that responses to chemosensory stimuli are related to sex, while the side of stimulation does not play a major role in the presently used paradigm. Finally, these data establish the lateralization paradigm as a psychophysical tool to investigate intranasal trigeminal function. SIGNIFICANCE: The present results obtained in a representative group of healthy subjects establishes a comprehensive set of data, which will serve as reference for future work in this area of research.     

Cerebrocortical Fos expression following dopaminergic stimulation: D1/D2 synergism and its breakdown

Using standard immunohistochemical techniques, we examined Fos expression in different areas and layers of cerebral cortex in rats following combined or separate stimulation of dopamine D1 and D2 receptors under normal conditions and following five days of reserpine (1 mg/kg/day), a treatment that causes a breakdown in requisite D1/D2 synergism. In normal animals, combined but not separate stimulation of D1 and D2 receptors elicited Fos expression in frontal and parietal, but not cingulate, cortex. Expression was highest in layer IV of primary somatosensory cortex; in frontal and secondary somatosensory cortex, Fos expression was lower and peaked in layer VI. Cortical Fos expression following amphetamine showed the same general pattern, and was blocked by either a selective D1 or D2 antagonist. Following reserpine treatment, stimulation of either D1 or D2 receptors gave rise to cortical Fos expression in patterns similar to each other and to combined D1/D2 stimulation in normal rats (except in frontal cortex in which separate D1 or D2 stimulation was unable to elicit Fos even following repeated reserpine treatment). The fact that cortical Fos expression was tightly associated with behavioral activation together with its laminar and areal distribution suggest that sensory input resulting from behavioral activation may be an important: stimulus for this immediate-early gene response.     

Cerebral chemosensory evoked potentials elicited by chemical stimulation of the human olfactory and respiratory nasal mucosa

A stimulation method was employed by which chemosensory evoked potentials were recorded without tactile somatosensory contamination. The purpose of the study was to determine whether potential components evoked by stimulation of the chemoreceptors of the trigeminal nerve can be distinguished from those of the olfactory nerve. The stimulants (vanillin, phenylethyl alcohol, limonene, menthol, anethol, benzaldehyde, carbon dioxide and a mixture of vanillin and carbon dioxide) were presented in a randomized order to 13 volunteers. Chemosensory evoked potentials to substances which anosmics are unable to perceive (vanillin, phenylethyl alcohol) were termed olfactory evoked potentials; potentials to CO2, which effected no olfactory sensations were termed chemo-somatosensory potentials. Analysis of variance revealed that the different substances resulted in statistically significant changes in the amplitudes and latencies of the evoked potentials, and also in the subjective estimates of intensity. An increased excitation of the somatosensory system resulted in reduced latencies and enhanced amplitudes of the evoked potentials. Responses to the mixture of carbon dioxide and vanillin appeared significantly earlier (50-150 msec) than responses to either substance alone.     

Sensory mapping in a congenitally deaf subject: MEG and fRMI studies of cross-modal non-plasticity

It has been proposed that the auditory cortex of deaf subjects may provide an example of cross-modal compensatory plasticity. We investigated whether sensory stimulation could elicit responses from auditory areas of a congenitally deaf subject. Neuromagnetic fields were recorded using a 37-channel biomagnetometer under conditions of: 1) visual stimulation; 2) somatosensory stimulation; and 3) a simple motor task. Visual items were reversing checkerboards and single light spots, presented in various portions of the visual field; somatosensory stimuli were pneumatic taps delivered to individual digit-segments and the lip; the motor task was self-paced finger tapping. In addition, functional magnetic resonance imaging was used to observe the activation elicited by full-field checkerboard and sign language stimuli. No responses to passively presented visual or somatosensory stimuli were observed in the auditory cortex. In contrast, somatosensory, motor, and visual cortices revealed evoked magnetic responses comparable to those from control subjects, indicating canonical anatomic and physiological organization in these areas. These data suggest that primary projection areas do not reveal obvious plastic effects. We suggest that in the human auditory cortex compensatory plasticity emerges primarily as a property of non-primary areas and is best observed under attentionally demanding conditions. Hum. Brain Mapping 5:437–444, 1997. © 1997 Wiley-Liss, Inc.     

Functional magnetic resonance imaging and somatosensory evoked potentials in rats with a neonatally induced freeze lesion of the somatosensory cortex.

Brain plasticity is an important mechanism for functional recovery from a cerebral lesion. The authors aimed to visualize plasticity in adult rats with a neonatal freeze lesion in the somatosensory cortex using functional magnetic resonance imaging (fMRI), and hypothesized activation outside the primary projection area. A freeze lesion was induced in the right somatosensory cortex of newborn Wistar rats (n = 12). Sham-operated animals (n = 7) served as controls. After 6 or 7 months, a neurologic examination was followed by recording of somatosensory evoked potentials (SSEPs) and magnetic resonance experiments (anatomical images, fMRI with blood oxygen level-dependent contrast and perfusion-weighted imaging) with electrical forepaw stimulation under alpha-chloralose anesthesia. Lesioned animals had no obvious neurologic deficits. Anatomical magnetic resonance images showed a malformed cortex or hyperintense areas (cysts) in the lesioned hemisphere. SSEPs were distorted and smaller in amplitude, and fMRI activation was significantly weaker in the lesioned hemisphere. Only in a few animals were cortical areas outside the primary sensory cortex activated. The results are discussed in respect to an apparent absence of plasticity, loss of excitable tissue, the excitability of the lesioned hemisphere, altered connectivity, and a disturbed coupling of increased neuronal activity to the hemodynamic response.     

Primary somatosensory cortex is actively involved in pain processing in human

We recorded somatosensory evoked magnetic fields (SEFs) by a whole head magnetometer to elucidate cortical receptive areas involved in pain processing, focusing on the primary somatosensory cortex (SI), following painful CO(2) laser stimulation of the dorsum of the left hand in 12 healthy human subjects. In seven subjects, three spatially segregated cortical areas (contralateral SI and bilateral second (SII) somatosensory cortices) were simultaneously activated at around 210 ms after the stimulus, suggesting parallel processing of pain information in SI and SII. Equivalent current dipole (ECD) in SI pointed anteriorly in three subjects whereas posteriorly in the remaining four. We also recorded SEFs following electric stimulation of the left median nerve at wrist in three subjects. ECD of CO(2) laser stimulation was located medial-superior to that of electric stimulation in all three subjects. In addition, by direct recording of somatosensory evoked potentials (SEPs) from peri-Rolandic cortex by subdural electrodes in an epilepsy patient, we identified a response to the laser stimulation over the contralateral SI with the peak latency of 220 ms. Its distribution was similar to, but slightly wider than, that of P25 of electric SEPs. Taken together, it is postulated that the pain impulse is received in the crown of the postcentral gyrus in human.     

Topographical differences in the trigeminal sensitivity of the human nasal mucosa

The aim of the study was to investigate differences in the distribution of intranasal trigeminal receptors in humans using an electrophysiological measure of trigeminally induced activation, the negative mucosa potential. A total of 29 young, healthy volunteers participated, results were on the basis of data from 18 participants. The trigeminal irritant CO2 was presented using a computer-controlled olfactometer. Negative mucosa potential recording sites included the anterior olfactory cleft, the anterior septum, and the lower turbinate. Lowest amplitudes of the negative mucosa potential were found in the olfactory cleft, maximum amplitudes at the septum. Intranasal measurements of CO2 concentrations suggested that these differences were not due to the intranasal distribution of CO2. These results are compatible with the idea that the trigeminal system acts as a sentinel of the human airways.     

Activation of olfactory and trigeminal cortical areas following stimulation of the nasal mucosa with low concentrations of S(-)-nicotine vapor--an fMRI study on chemosensory perception

Applied to the nasal mucosa in low concentrations, nicotine vapor evokes odorous sensations (mediated by the olfactory system) whereas at higher concentrations nicotine vapor additionally produces burning and stinging sensations in the nose (mediated by the trigeminal system). The objective of this study was to determine whether intranasal stimulation with suprathreshold concentrations of S(-)-nicotine vapor causes brain activation in olfactory cortical areas or if trigeminal cortical areas are also activated. Individual olfactory detection thresholds for S(-)-nicotine were determined in 19 healthy occasional smokers using a computer-controlled air-dilution olfactometer. Functional magnetic resonance images were acquired using a 1.5T MR scanner with applications of nicotine in concentrations at or just above the individual's olfactory detection threshold. Subjects reliably perceived the stimuli as being odorous. Accordingly, activation of brain areas known to be involved in processing of olfactory stimuli was identified. Although most of the subjects never or only rarely observed a burning or painful sensation in the nose, brain areas associated with the processing of painful stimuli were activated in all subjects. This indicates that the olfactory and trigeminal systems are activated during perception of nicotine and it is not possible to completely separate olfactory from trigeminal effects by lowering the concentration of the applied nicotine. In conclusion, even at low concentrations that do not consistently lead to painful sensations, intranasally applied nicotine activates both the olfactory and the trigeminal system.     

Phantom digit somatotopy: a functional magnetic resonance imaging study in forearm amputees

Forearm amputees often experience non-painful sensations in their phantom when the amputation stump is touched. Cutaneous stimulation of specific stump areas may be perceived as stimulation of specific phantom fingers (stump hand map). The neuronal basis of referred phantom limb sensations is unknown. We used functional magnetic resonance imaging to demonstrate a somatotopic map of the phantom fingers in the hand region of the primary somatosensory cortex after tactile stump stimulation. The location and extent of phantom finger activation in the primary somatosensory cortex corresponded well to the location of normal fingers in a reference population. Stimulation of the stump hand map resulted in an increased bilateral activation of the primary somatosensory cortex compared with stimulation of forearm regions outside the stump hand map. Increased activation was also seen in contralateral posterior parietal cortex and premotor cortex. Ipsilateral primary somatosensory cortex activation might represent a compensatory mechanism and activation of the non-primary fronto-parietal areas might correspond to awareness of the phantom limb, which is enhanced when experiencing the referred sensations. It is concluded that phantom sensation elicited by stimulation of stump hand map areas is associated with activation of finger-specific somatotopical representations in the primary somatosensory cortex. This suggests that the primary somatosensory cortex could be a neural substrate of non-painful phantom sensations. The stump hand map phenomenon might be useful in the development of prosthetic hand devices.     

Role of anterior pretectal nucleus in somatosensory cortical descending modulation of jaw-opening reflex in rats

Both the somatosensory cerebral cortex and anterior pretectal nucleus (APT) have been shown to produce descending modulation of trigeminal (V) and spinal somatosensory neurone and reflex activities. Since the APT receives a direct projection from the somatosensory cortex, experiments were performed to compare the effects of APT and somatosensory cortex stimulation on the jaw-opening reflex (JOR) and to examine the possible involvement of APT in corticofugal modulation. Conditioning stimulation of the ipsilateral or contralateral somatosensory cortex in chloralose-urethane anaesthetized rats induced inhibition of the JOR elicited by test stimulation of the maxillary skin or tooth pulp, at conditioning-test intervals between 30 and 200 ms. A similar time course of inhibition of the JOR was noted with APT conditioning stimulation. Local unilateral injection of 2% lidocaine (0.3-0.6 microliter) into APT could partially and reversibly reduce the ipsilateral cortically evoked inhibition of the JOR. Ibotenic acid (5 micrograms, 0.5 microliter)-induced unilateral lesions of APT and its adjoining structures also greatly reduced the ipsilateral cortically induced inhibition of the JOR. Histological reconstruction of APT lesion sites and data analysis indicated that this reduction in the corticofugal inhibition was proportionally and significantly related to the extent of damage to APT, but not to its adjoining structures. These findings collectively suggest that the cortically-induced inhibition of the JOR is at least partly mediated by a relay in the APT.     

The corticotrigeminal projection in the cat. A study of the organization of cortical projections to the spinal trigeminal nucleus

The projection from the cerebral cortex to the spinal trigeminal nucleus has been studied light microscopically in adult cats. Both orthograde degeneration and orthograde intra-axonal labeling techniques have been applied. Our results indicate that the projection from the coronal gyrus (face area of primary somatosensory cortex) to the spinal trigeminal complex is somatotopically organized. In subnucleus caudalis this somatotopy is organized dorsoventrally and appears to match the somatotopic distribution of the divisional trigeminal afferents. Hence cortical fibers originating from the posterior coronal gyrus (upper representation) project ventrolaterally into caudalis where division I trigeminal afferents terminate. Likewise cortical fibers from the anterior coronal gyrus (jaw and tongue representation) terminate dorsomedially in caudalis to overlap with division III trigeminal afferents. In contrast, the distribution of corticofugal afferents to the rostral spinal trigeminal subnuclei (pars interpolaris and oralis) is organized mediolaterally. Therefore in these subnuclei the cortical projection does not appear to overlap the dorsoventral lamination of the divisional trigeminal afferents. In addition, our results suggest that the cortical projection to subnucleus caudalis includes fibers which terminate in the marginal zone (lamina I) and its extensions into the spinal trigeminal tract (the interstitial cells of Cajal). We have been unable to document a projection from the proreate gyrus to the spinal trigeminal complex.     

Chemosensory processing in children with attention-deficit/hyperactivity disorder

BackgroundIn attention-deficit/hyperactivity disorder (ADHD) not only deficits in dopamine-related cognitive functioning have been found but also a lower dopamine-sensitive olfactory threshold. The aim of the present study was to proof that only olfactory but not trigeminal sensitivity is increased in ADHD. Structural magnetic resonance imaging (MRI) was used to show increased olfactory bulb (OB) volume- a structure which is strongly shaped by olfactory performance through the mechanism of neuroplasticity (e.g. synaptogenesis). To elucidate whether cortical mechanisms are involved in altered olfaction in ADHD, functional MRI (fMRI) was introduced.MethodsA total of 18 boys with ADHD and 17 healthy controls (aged 7–12) were included in the study. Olfactory as well as trigeminal detection thresholds were examined. OB sizes were measured by means of structural MRI and an analysis of effective functional (fMRI) coupling of primary olfactory cortex was conducted. The frontal piriform cortex (fPIR) was chosen as seed region because of its importance in processing both trigeminal and olfactory stimuli as well as having profound influence on inner OB-signaling.ResultsIncreased olfactory sensitivity as well as an increase in OB volume was found in ADHD. There were no group differences in sensitivity towards a trigeminal stimulus. Compared to healthy controls, the fPIR in ADHD was more positively coupled with structures belonging to the salience network during olfactory and, to a lesser extent, during trigeminal stimulation.ConclusionsOlfactory functioning is superior in subjects with ADHD. The observed increase in OB volume may relate to higher olfactory sensitivity in terms of neuroplasticity. During the processing of chemosensory stimuli, the primary olfactory cortex in ADHD is differently coupled to higher cortical structures which might indicate an altered top-down influence on OB structure and function.     

Neurofunctional disturbances as related to cortical ischemia and white matter ischemia

We evaluated regional cerebral blood flow (rCBF) by means of hydrogen clearance method as well as [14C]-iodoantipyrine autoradiographic method, cortical auditory evoked potentials (AEP), somatosensory evoked potentials (SEP) induced by forelimb (median nerve) stimulation (SEP-F), and SEP induced by hindlimb (tibial nerve) stimulation (SEP-H) in cats after occlusion of the left middle cerebral artery (MCA) under alpha-chloralose anesthesia. According to the degree of ischemia, the experimental animals were divided into two groups. One was the critical ischemia which was defined as permanent total suppression of AEP, and low residual blood flow in the auditory cortex. And the other was the non-critical ischemia which included transient suppression and spontaneous recovery of the cortical sensory evoked potentials, and high residual blood flow (greater than 15 ml/100 g/min). In one cat with transient suppression of three kinds of sensory evoked potentials, the [14C]-iodoantipyrine (IAP) autoradiograph revealed only a limited ischemic area of subcortical white matter. In the critical ischemia group, ischemia of the primary sensory cortex ranged from the mostly affected primary auditory cortex (supplied by the MCA) to the least affected hindlimb projection area within primary somatosensory cortex (supplied by the ACA). The forelimb projection area of the primary somatosensory cortex (supplied by both ACA and MCA) showed a mild or moderate reduction of rCBF after occlusion. The [14C]-IAP autoradiograph showed severe reduction of the white matter including the somatosensory pathway in the wide range. However, rCBF in the thalamus and hindlimb projection area within somatosensory cortex was almost intact in the cat with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of graded hypercapnia on the activation flow coupling response due to forepaw stimulation in alpha-chloralose anesthetized rats

Activation flow coupling (AFC), changes in cerebral blood flow (CBF) due to changes in neural activity with functional stimulation, provides the physiological basis of many neuroimaging techniques. Hypercapnia leads to an increase in CBF while neural activity remains unaffected. Laser Doppler (LD) flowmetry was used to measure CBF changes (LD(CBF)) in the somatosensory cortex due to periodic electrical forepaw stimulation (4 s in duration) before and during graded hypercapnia (3% CO(2), 5% CO(2) and 10% CO(2)). With increasing CO(2) concentrations, the baseline LD(CBF) progressively increased. The peak height (PH) of the LD(CBF) response, expressed as a percent change from the observed baseline for each hypercapnic state, significantly decreased (P<0.05) with increasing CO(2) concentrations. However, the absolute magnitude of the LD(CBF) change was independent of CO(2) concentration. The temporal dynamics of the LD(CBF) response during hypercapnia were significantly prolonged compared to baseline conditions (P<0.05).     

Cortical deafferentation in cat focal ischemia: disturbance and recovery of sensory functions in cortical areas with different degrees of cerebral blood flow reduction

During and after 15-min occlusion of the middle cerebral artery (MCA) in cats, local CBF and neuronal activity were measured in cortical areas varying in the degree of CBF reduction. In an area within the ischemic center (primary auditory cortex, middle ectosylvian gyrus), CBF was severely suppressed. Click-induced auditory evoked potentials and evoked as well as spontaneous single-unit activity ceased within 1 min after occlusion. Recirculation resulted in a recovery of the different neurophysiological parameters with a time delay ranging from several minutes to 2 h. In two areas surrounding the ischemic focus (a visual area in the marginal gyrus and the forelimb representation area in the primary somatosensory cortex), CBF was reduced but remained above 30 ml/100 g/min during MCA occlusion. Visual flash-induced evoked potentials and somatosensory evoked potentials induced by median nerve electrical stimulation ceased in the corresponding areas with a somewhat slower time course as compared to the auditory responses and they recovered faster after recirculation. In another somatosensory area (hindlimb projection area in the primary somatosensory cortex), CBF stayed nearly at control levels during occlusion. Evoked potentials and single-unit activity induced by tibial nerve electrical stimulation decreased approximately 5 min after occlusion and were abolished approximately 5 min later. At that time, single-unit activity had changed to a nonresponsive pattern but persisted. However, potentials evoked transcallosally by electrical stimulation of the contralateral hemisphere were still recorded. After reopening the MCA, the recovery of neuronal functions was usually complete and occurred within approximately 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional connectivity between somatosensory and visual cortex in early blind humans

Crossmodal plasticity occurs when loss of input in one sensory modality leads to reorganization in brain representations of other sensory modalities. In congenital blindness the visual cortex becomes responsive to somatosensory input such as occurs during Braille reading. The route by which somatosensory information reaches the visual cortex is not known. Here, we used repetitive transcranial magnetic stimulation (rTMS) to probe the connection between primary somatosensory cortex (S1) and early visual cortex (V1 and neighboring areas), combining rTMS with positron emission tomography (PET). We applied stimulation over S1 in sighted, early blind and late blind individuals. Baseline regional cerebral blood flow in occipital cortex was highest in early blind and lowest in late blind individuals. Only the early blind group showed significant activation of early visual areas when rTMS was delivered over S1. This activation was significantly higher in early than in late blind, but not relative to sighted controls. These results are consistent with the hypothesis that tactile information may reach early visual areas in early blind humans through cortico-cortical pathways, possibly supporting enhanced tactile information processing.