ORAL SESSIONS: MOTOR AND SENSORY

Finger movement in children: less distinct neocortical activationprofiles and reduced cerebellar involvement compared to adults

Ralph-Axel Miiller, Otto Muzik, Robert D. Rothermel, Michael E. Behen, RyanDowney, Pulak K. Chakraborty & Harry T. Chugani

Children's Hospital ofMichigan, Wayne State University, Detroit, MI48201, USA

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Intracranial mapping data suggest that the brain organization for motor control in children differs from that inadults, possibly in the sense ofless focalized neural substrates (1). Developmental and skill-related focalization ofactivations has been documented for non-motor domains as well (2-4). In addition, there is evidence of cerebellarinvolvement in overlearned skills, presumably due to specific learning potentials in the cerebellum (5-7). In thepresent study, we compared activations for finger movement of the unaffected hand in children and adults withunilateral lesion. In view of the lack of normative data for children, these data were considered pseudonormal. Wehypothesized that in adults, when compared to children, (a) developmental focalization would be reflected ingreater activation in motor and greater deactivation in non-motor cortex, and (b) cerebellar activations would bemore pronounced.

MethodsTen children (aged 6-15y) and 14 adults (aged 18-74y) with unilateral lesion were studied by means of [150]-waterPET. Regional cerebral blood flow (rCBF) was studied for rest and finger-thumb tapping of the hand ipsilateral tothe lesion. Each condition was scanned twice in each patient with a Siemens Exact HR scanner. Images were co­registered, normalized, and subtracted (movement minus rest) intraindividually, using the Minoshima et a1. pack­age (8). Mean rCBF changes were computed for 3 regions of interests (ROIs): motor (Brodmann areas [BAs] 1-6),non-motor (BAs 20-23, 26-31, 34-39), and cerebellar e -r----- -----------...,(hemispheres, deep nuclei, and the vermis). The motorand non-motor ROIs were only analyzed for thehemisphere contralateral to the movement (i.e. for thenon-lesional hemisphere). Expected group differenceswere evaluated by means of a one-tailed t-Test,

ResultsThe motor ROI showed the expected greater meanactivation in the adults than the children, but thedifference was not significant (see figure on the right).However, greater deactivation in the non-motor ROI inadults was found as expected and came very close tosignificance (p=.056). Also, as expected, cerebellaractivations were significantly (p<.05) greater in theadults than in the children.

ConclusionsFinger movement in children is associated with activations in contralateral motor cortex similar to those found inadults (e.g., 9). This corresponds to previous findings by Popp et a1. (10). However, our hypothesis ofdevelopmental focalization was supported by the much more pronounced deactivation of temporo-parietal non­motor cortex in adults as compared to children. This suggests that fine motor related activation/deactivationprofiles are more distinct in adults than in children. In addition, the expected greater cerebellar activation in adultsduring finger movement was found to be robust and significant. A possible explanation is that the cerebellumbecomes more importantly involved in motor and non-motor cognitive functions in the mature brain. This maybe related to findings indicating a greater cerebellar potential for language involvement in adults than in childrenfollowing left-hemisphere lesion (11).

ReferencesI. Duchowny, M, Jayakar, P, in Electrical and Magnetic Stimulation of the Brain and Spinal Cord O. Devinsky, A.

Beric, M. Dogali, Eds. (Raven Press, 1993) 149-54.2. Haier, RJ, Siegel, BV, MacLachlan, A, Soderling, E., Lottenberg, S, et al. Brain Res 1992, 570: 134-43.3. Mills, DL, et al. in Human behavior and the developing brain G Dawson Ed. (Guilford, 1994) 427-455.4. Raichle, ME, Fiez, JA, Videen, TO, MacLeod, A-MK, Pardo, JV, et al. Cereb. Cortex 1994,4: 8-26.5. Black, JE, Isaacs, KR, Anderson, BJ, Alcantara, AA, et al. Proc. Natl. Acad. Sci. USA 1990, 87: 5568-72.6. Leiner, HC, Leiner, AL, Dow, RS Human Brain Mapping 1995,2: 244-254.7. Raymond, JL, Lisberger, SG, Mauk, MD Science 1996, 272: 1126-1131.8. Minoshima, S, et al. in Quantification of Brain Function K. Uernura, Ed. (Elsevier, 1993) 409-15.9. Colebatch, JG, Deiber, M-P, Passingham, RE, Friston, KJ, et al. J. Neurophysiol. 1991,65: 1392-1401.10. Popp, CA, Trudeau, JD, Durden, D, Faber, TL, Burrows, B, et al. Neuroimage 1996,3: S594.II. MUller, R-A, Rothermel, RD, Behen, ME, Muzik, 0, Mangner, TJ, Chugani, HT submitted.

S11

ORAL SESSIONS: MOTOR AND SENSORY

The time-course of activity in motor areas during motor learningR.E.Passingham, I.Toni, M.Krams, R.Turner, J.Ashburner, K.Friston

WDCN, Institute of Neurology, London, U.K.

IntroductionIn previous studies we have used PET to scan subjects during new learning and automatic performance of amotor sequence (1). We have now exploited fMRI to scan subjects continuously for 40 minutes while theylearn and continuously perform a motor sequence. This enables us to plot the time-course of the activations inall those areas that are involved in such motor learning.

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MethodsThree subjects were scanned on a Siemens VISIONscanner operating at 2T. Data were acquired using T2*­weighted EPI (TE=40ms, TR=6.4s, 64 slices, 3x3x2mm voxels). 376 volumes were acquired during thealternated performance of an activation condition and abaseline condition. In the activation condition, thesubjects had to learn by trial and error a sequence offinger movements, 8 moves long, using their right hand.Visual patterns were presented on each trial to paceperformance at 0.31 Hz. After each movement visualfeedback cues informed the subjects whether themovement was correct or not. In the baseline condition,the subjects were presented with irrelevant visual patternsand feedback cues, but they made no movements. Eachbaseline period lasted 25.6 s (TR*4), whereas the lengthof the activation period was determined by the number oferrors made by the subject (range: from 51.2 s to 25.6 s).The activation-baseline pattern was modeled using asquare wave function. Changes over time associated withmotor learning were modeled with a set of Fourier seriesorthogonalised to the square wave function. Statisticalanalysis was performed using SPM96.

ResultsThe time-course of changes in activation differed indifferent brain regions. There was a considerableincreaseinactivation of thepremotor cortex early in learning, whereasthe activation of the postcentral gyrus was relativelyunchangedthroughout the periodof scanning (fig. lA). Theactivation for the dorsal prefrontal and anterior cingulatecortexdecreasedearlierthan that ofpremotor cortex, reachingbaselinelevelsroughly attwothirdof thescan time (fig.IB),at a time when subjects report the task to be becomingautomatic. The activity of the contralateral cerebellumincreased only during the initial phase of learning,whereas the ipsilateral cerebellum showed a sustainedactivation till the task became overlearned (fig.lC).

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Figure 1. Time courses of activation for differentbrain regions. The plottedvaluesrepresentthedifferencebetween the fitted response of each activation epochand the successive baseline epoch.

ConclusionThe ability to use tMRI to charts changes over time mayenable one to relate changes in different areas to differentaspects of learning.

Reference1. Jenkins, LH. et a1. J. Neurosci. 1994, 14, 3775-3790

to 15 ZO 2S 30 35 40min

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ORAL SESSIONS: MOTOR AND SENSORY

Distributed Neural Systems Underlying the Timing of MovementsS.M. Raot, D.L. Barrington2,K.V. Baaland2

, J.A. Bobholzt, R.W. Cox', J.R. Binder!'Medical College ofWisconsin, Milwaukee, WI and

2Veterans Affairs Medical Center, Albuquerque, NM, USA.

The capacity to precisely time movement sequences is critical for the performance of skilled actions. Thenovice musician, for example, will initially rely on a metronome to maintain a specified rhythm, but withexperience develops an internalized timing standard. Most studies have investigated internal timekeepingoperations for long duration periods (greater than 1 sec). In the present FMRI study, the timing of relativelyshort duration intervals was investigated because these are most likely involved in the programming of skilledactions.

Subjects and Activation ConditionsThirteen strongly right-handed healthy volunteers (IOF/3M, mean age 23.2 yrs, range 18-31 yrs) were studied.Informed consent was obtained according to institutional guidelines established by the MCW Human SubjectsReview Committee. Subjects performed a series of four consecutive activation conditions consisting of twoexperimental (Synchronization, Continuation) and two control (Listening, Discrimination) tasks, which werepreceded and followed by a rest period. In the Synchronization (S) condition, subjects made right index fingerkeypresses in time with a series of tones separated by a constant interval of either 300 or 600 ms. During theContinuation (C) condition, subjects were instructed to maintain the same tapping rate, but without benefit ofthe pacing tone. The Listening (L) condition required subjects to passively attend to the same pacing tonepresented in the S condition, but were instructed not to tap their finger. The L condition controlled for theauditory sensory perception of the tone sequences in the S condition. In the Discrimination (0) condition,subjects listened to a series of tone pairs separated by 300 or 600 ms and pressed a key with their right indexfinger whenever a transition in pitch occurred (high to low or low to high). The D condition controlled for theauditory sensory perception in the S condition) and the response execution processes in the S and C conditions.

Functional MRIFMRI was conducted on a 1.5T GE Signa scanner equipped with a 30.5 em i.d. 3-axis local gradient coil andan endcapped quadrature birdcage RF coil, using a blipped gradient-echo echo-planar pulse sequence (TE=40ms; FOV=24 em; 64 x 64 matrix; 3.75 mm resolution). Twenty-two contiguous saggital slices (6 mm slicethickness) covering the entire brain were collected with a TR=4.5 s; 104 consecutive images were collected ineach imaging series. A series consisted of 5 cycles of rest and "activation," with each cycle beginning andending with an 18-s rest period. The activation period consisted of the four consecutive 18-s epochs, duringwhich subjects performed the S, C, L, and D conditions in a fixed order. Subjects underwent six functionalimaging series, three each at the 300 and 600 ms pacing intervals. Minor anatomic distortions in the EPimages due to local field inhomogeneities were corrected using a field map. Each image time series wasspatially registered in-plane to reduce the effects of head motion. Linear drift in the time series was removedusing a regression analysis. Functional images were created by generating statistical parametric maps (SPMs)of t-deviates reflecting differences between the condition and the rest states at each voxel location for eachsubject. Individual anatomical (SPGR) scans and SPMs were linearly interpolated to volumes with I mm"voxels, co-registered, and transformed into stereotaxic space using the "MCW-AFNf' software package.

Results and DiscussionReaction time results demonstrated that the subjects were able toreproduce the timing intervals with a high degree of accuracy. Bothcontrol conditions produced bilateral activation of the superior temporalgyrus, and the D condition also activated the rostral supplementary motorarea (SMA). Both the S and C conditions produced equivalent activationwithin the left sensorimotor cortex (SMC), right cerebellum (dorsaldentate nucleus), and right superior temporal gyrus. Only the C conditionproduced additional activation of a medial premotor system, including thecaudal SMA, left putamen, and left ventrolateral thalamus (see figure).The C condition also activated a region within the right inferior frontalgyrus, which is functionally interconnected with auditory cortex. Theseresults indicate that internal timing is dependent on 3 distributed neuralsystems, one involved in explicit timing, one that mediates auditoryworking memory, and another involved in sensorimotor processing.

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ORAL SESSIONS: MOTOR AND SENSORY

Coding the Motor Significance of Sensory Stimuli in PosteriorParietal Cortex

Marco Iacoboni, Roger P. Woods, John C. MazziottaUCLA Brain Mapping Division, Los Angeles, CA, USA

Introduction. The posterior parietal cortex is a critical cortical region for sensorimotor integration. It is unclearwhether sensorimotor integration in posterior parietal areas is driven more by the sensory-attentional or by themotor-intentional component. Here we present data from positron emission tomography suggesting that someposterior parietal areas code the motor/intentional significance of sensory stimuli.Methods. We studied 13 right-handers with PET and HZ

150, using a Siemens/CTl 831-08 tomograph modified for3D data acquisition and reconstruction. A full description of PET methods is provided elsewhere.' Seven subjectsparticipated in an auditory version of the experiment and the other six subjects participated in a visual version.Subjects had two response conditions. In the compatible response condition, subjects were told to respond tolateralized sensory stimuli (auditory tones in the auditory version and light flashes in the visual version) with theipsilateral hand. In the incompatible response condition, subjects were told to respond to left or right sensory stimuliwith the contralateral hand. Auditory and visual stimuli were counterbalanced in the two hemispaces and presentedevery 1.25 sec, regardless of the response time of the previous trial. This kept the number of sensory stimuli andmotor responses constant in each scan in each subject. The position in space of auditory and visual stimuli largelydiffered between the two versions of the experiment. The significance of the sensory stimuli for motor behavior,however, was invariant across the two experiments.Results. As expected, errors were rare (-2%) and not different between stimulus modality, response conditions, andresponse hands. Compatible responses were 52 ms faster than incompatible responses, for both auditory (p<O.OOOI)and visual (p<O.OOO5) stimuli. PET images of the subjects participating in both auditory and visual versions of theexperiment were registered in a common space. Incompatible responses, when compared to compatible responses,produced significant rCBF increases (p<.05, corrected for multiple spatial comparisons) in two left posterior parietalareas in both auditory and visual versions of the experiment (see Figure).

400

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D Compatible ~ Incompati ble

Graphs: From left to right: Reaction times (RT) and normalized counts in the intraparietal sulcus area (IPS) andtransverse parietal sulcus area (TPS) for the two response conditions to visual and auditory stimuli. Images:Posterior parietal areas located in the intraparietal sulcus and in the transverse parietal sulcus and activated in bothvisual and auditory versions of the experiment. The MRI of a single subject located in the common stereotaxic spaceis used for display purposes.

Discussion. The two posterior parietal areas reported here are similarly activated by stimuli of different modalities(auditory and visual) with different spatial locations but having similar instructional significance for motor behavior.It follows that these two areas code the significance of external stimuli for spatial motor behavior, which is invariantacross the two versions of the experiment, rather than the specific characteristics of external stimuli or their locationin space. Spatial attention to left and right hemispace is also invariant in the two versions of the experiment, raisingthe possibility that the common activations are due to attentional mechanisms. However, there is evidence forseparate neural systems in the parietal cortex for visual and auditory attention-, and there is no empirical evidenceand no model of spatial attention suggesting that the left posterior parietal cortex independently subserves spatialattention in both hemispaces (stimuli were counterbalanced in left and right hemispace). Thus, the spatial attentionhypothesis is unlikely. In conclusion, these data, in line with some lesion data in macaques and humans-:", suggesta role of the posterior parietal cortex in coding the significance for action of sensory stimuli.References1. Iacoboni, M., Woods, R.P. & Mazziotta, J.e. J. Neurophysiol. 76, 321-331 (1996).2. Sieroff, E. & Michel, F. Neuropsychologia 25,907 (1987).3. Halsband, U. & Passingham, R. Brain Res. 240, 368-372 (1982).4. Perenin, M.-T. & Vighetto, A. Brain 111, 643-674 (1988).

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ORAL SESSIONS: MOTOR AND SENSORY

Acupuncture Modulating The Limbic Brain Detected by Functional MR Imaging

M.-T. WU!36, J. Xiong", P.-c. Yang''", J.-c. Hsieh56, G. Tsai7, B. R. Rosen", K. K. Kwong!

1 MGH -NMR Center, Charlestown, MA; 2 MEEI, Boston, MA; 3 Dept. ofRadiology, "Psychiatry , Kaohsiung VeteransGeneral Hospital, Kaohsiung, Taiwan;5 Dept. ofAnesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan;

6 National Yang-Ming University, Taipei, Taiwan; 7 Dept. ofPsychiatry, MGH, Boston, MA

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Recent advances of acupuncture researches suggest that the analgesic effect of acupuncture results from the centralmodulation of pain perception mediated by endorphins, which can occur on several levels of the ascending painpathway: the spinal cord, the midbrain, the hypothalamus and the thalamus. However, the role of cerebral cortex inacupuncture analgesia is still unclear.

The limbic brain is known to convey the affective-cognitive aspects of pain perception through the medial ascendingpathway. Among the main limbic components, the hypothalamus, nucleus accumbens, amygdala and hippocampushave been implicated in the neural circuitry mediating acupuncture analgesia.

We hypothesized that central processing of acupuncture stimulation involves the modulation of neuronal structuresrelated to the multiple dimensions of pain. We applied fMRI to investigate this hypothesis.Subjects And Methods: Two stimulation paradigms on a blinded, balanced crossover design were performed by anacupuncturist on nine right-handed healthy subjects: (1) acupuncture stimulation; inserting an acupuncture needle intoleft leg acupoint Zusanli (St.36) and manipulating around once per second and (2) pricking cutaneous pain stimulation:repeatedly pricking the skin over Zusanli with the needle tip once per second. Each paradigm comprised off-on-off-on­off epochs and last for 8 minutes. Psychophysical responses to the pain intensity, De Qi (the acupuncture needlesensation) intensity, spreading of pain or De Qi, unpleasantness and anxiety, as well as changes of heart rate and end­tidal CO2 were assessed. fMRI using gradient echo sequence covering the bilateral hemispheres was obtained on a 1.5 Techo planar imager. The data were motion corrected, Talairach-transformed, averaged across 9 subjects and evaluatedby Kolmogorov-Smirnov test (threshold p < 10.4

) .

Results: Multivariate ANOV A showed acupuncture caused more De Qi, spreading of somatosensory sensation, morebradycardia, less pain intensity and equivalent anxiety and unpleasantness than did pricking cutaneous pain. fMRI ofacupuncture showed: (1) increased signal in the hypothalamus and nucleus accumbens contralaterally. (2) decreasedsignal in the hippocampus, rostral part of anterior cingulate cortex (ACC), prefrontal cortex (PFC) and superiorposterior parietal cortex (PPC) bilaterally, amygdala contralaterally and caudate nucleus ipsilaterally In contrast. thepricking cutaneous pain caused increased signal in the primary somatosensory, thalamus, posterior-caudal part of ACesupplementary motor area contralaterally, putamen ipsilaterally and second somatosensory cortex, insula, PFC andPPC bilaterally; a pattern consistent with that reported in neuroimaging study of pain.Conclusion: Acupuncture stimulation modulates the limbic brain which may be associated with descendingantinociception and affective-cognitive aspects of pain perception.

(A) ap -4 mm (C) ap +8 mm (E) ap +32 mm

Figure Foci with increased signal during pricking cutaneous pain (A, B), acupuncture (C, D) and with decreased signal duringacupuncture (E, F). GC, cingulate gyrus. GFd, medial frontal gyrus. GFm, middle frontal gyrus. GPrC, precentral gyrus. Hi,hippocampus. Hy, hypothalamus. INS, insula. NACs, nucleus accumbens. SolI, secondary somatosensory. Th, thalamus. (G, H)showed representativetime-course of signal changes. Theblocks indicatestimulation periods

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ORAL SESSIONS: MOTOR AND SENSORY

Thalamic Stimulation for the Relief of Pain: Possible Modulatory CircuitsRevealed by PET

G.H. Duncan'r', R. Kupers", s. Marchand", J. Gybels, M.e. Bushnell'f1McConnell Brain Imaging Centre, Montreal Neurological Institute,

2Departments ofAnesthesiology, Physiology and DentistyMcGill University, Montreal, Canada

3Faculte de Medecine dentaire, Univ. Montreal, Montreal, Canada"Univ. Quebec en Abitibi-Temiscamingue, Quebec, Canada

IntroductionElectrical stimulation of the somatosensory thalamus for the relief of intractable neuropathic pain wasintroduced more than 20 years ago [1]. Despite numerous clinical reports describing pain relief, its successis unpredictable, and there is stilI no consensus about underlying analgesic mechanisms [2]. Thus, in orderto illuminate possible mechanisms underlying successful analgesic thalamic stimulation, we have chosen fivepatients who report continued pain relief with long-term use of thalamic stimulation and examined regionalchanges in cerebral blood flow (rCBF) produced by the electrical stimulation.MethodsRegional CBF was measured following bolus injections of H2

1SO in five chronic pain patients selected fortheir successful use of analgesic thalamic stimulation. Four scanning conditions were used: 1) pre­stimulation baseline, 2) I-min after onset of thalamic stimulation, 3) 30-min after onset of stimulation, and4) 5-min after termination of stimulation. Each patient was submitted to the same scanning sequence on twoconsecutive days (i.e., 8 scans/patient), and patients refrained from therapeutic stimulation for 12 hoursbefore each scanning session. Statistical brain maps were derived and global searches of the brain wereperformed. In addition, directed searches were performed in thalamus and in pain-related cortical regionspreviously observed to be activated by pain (SI, SII, anterior cingulate and insular cortices).ResultsPatients' ratings of pain were reduced during thalamic stimulation to 70% of those observed during the pre­stimulation period. Patients also reported both tactile and thermal paraesthesia during the electrical thalamicstimulation. During thalamic stimulation, there was an increase in rCBF in ventroposterior lateral (VPL)thalamus, in the target region of the implanted electrodes. The most activated region remote to the site ofdirect electrical stimulation was the anterior insular cortex (IC), an area that receives thermal informationfrom ventromedial posterior (VMpo) thalamus, near the site of electrical stimulation (Craig et aI, 1996).Directed searches also revealed some activation in SI cortex, a primary output target of VPL.ConclusionsThese data suggest that the activation of thalamo-cortical circuits involved in both thermal and tactileprocessing might be important for successful pain relief by thalamic stimulation. Whereas the originaltheoretical basis for analgesic thalamic stimulation involved activation of tactile pathways (VPL to SIcortex), our data support recent ideas that activation of thermal pathways (VMpo to IC cortex) can provideimportant pain modulation, particularly in patients with central neuropathic pain [3].References[1] G.J. Mazars. Surg. Neurol. 4:93-95, 1977.[2] G.H. Duncan, M.C. Bushnell and S. Marchand. Pain 45:49-59, 1991.[3] A.D. Craig, E.M. Reiman, A. Evans and M.e. Bushnell. Nature 384: 258-260, 1996.

Supported by the Canadian MRC and Medtronics Corporation.

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ORAL SESSIONS: MOTOR AND SENSORY

Pleasant Touch Activates the Orbitofrontal CortexE.T. Rolls*, S.Francis, R. Bowtell, A.S.Browning*, S.Clare, EiSmith' and F.McGlonet

Magnetic Resonance Centre, University of Nottingham; *Department of ExperimentalPsychology, University of Oxford; 'Unilever Research, Port Sunlight Laboratory, WirralThe aim of this study was to investigate whether brain regions activated by the affective aspects of touch could beidentified using tMRI. It is known that after the primary somatosensory cortical area, the somatosensory pathwayscontinue to the insula and thus to the amygdala and orbitofrontal cortex (1,2). It is not known where in this pathwaypositively affective (pleasant) aspects of touch are represented. For comparison, it is known in the taste system thatin non-human primates, the primary taste cortex in the insula represents the identity and intensity of taste, whereasthe secondary taste cortex, in the orbitofrontal region, represents the affective aspect of taste (3,4).This experiment was designed to allow comparison of the patterns of brain activation during application of apleasant, but soft touch (velvet) to the hand with those elicited by a more intense, but affectively neutral stimulus,produced by touching the hand with the end of a wooden dowel. The rationale for this choice of stimulus was thatthe intense, but neutral stimulus might more strongly activate parts of the somatosensory system concerned with theintensity and identification of somatosensory stimuli, whereas the more pleasant tactile stimulus would lead to greateractivation in the parts of the brain concerned with representing the pleasantness of the touch.

MethodsImaging was performed on four healthy subjects using a 3.0 T EPI scanner (5). T2*-weighted coronal images wereobtained with 12 mm slice thickness, 64 x 64 matrix size, in-plane resolution of 3 mm, 23 ms echo time andgradient switching frequency of 1.9 kHz. In this study, twelve multi-slice images were generated every 2 seconds.Pleasant touch was produced by velvet wrapped on a small wooden dowel, which was moved round the palm ofthe hand. The neutral touch was produced by the cut end of a 4.7 em diameter wooden dowel, whose exposed grainwas rotated against the palm of the hand. Each stimulus was applied for a time of 16 s, followed by a resting periodof 16 s, over a total of 32 cycles. After correction for motion, and application of spatial and temporal smoothing,significant changes of pixel intensity during stimulation from the average value measured during the rest periodswere detected using at-test thresholded at p=0.005. Anatomical localisation was achieved via two multi-slice echo­planar data sets acquired with isotropic 3 mm resolution on each subject using an inversion recovery sequence witheither grey (TI=1200ms) or white matter (TI=400ms) nulled.

ResultsActivation in the right (contralateral) somatosensory cortex (central and postcentral sulcus) had higher value forthe neutral touch (1.02± 0.08%, mean ± sem) compared with pleasant touch (0.87 ± 0.05%). There was a smallactivation of the left (ipsilateral) postcentral cortex was lower, with no significant difference between the pleasantand neutral stimuli. Significant activation was found in the lateral orbitofrontal cortex for both stimuli. In the leftorbitofrontal cortex there was a statistically significant difference between the magnitude of activation by thepleasant (3.7+/- 0.4%) and neutral (1.0+/-0.1 %) stimuli, with a p-value of 0.011. A smaller non-significantdifference was found in the right orbitofrontal cortex. No significant activation was found in the medial orbitofrontalcortex, an area implicated in the representation of olfactory stimuli (6). A two-way analysis of variance with onefactor: brain region (orbitofrontal cortex vs somatosensory cortex) and the other factor: type of stimulation (pleasantvs neutral) showed a significant interaction (F(l,3)=18.95, P=0.021). This indicates that the orbitofrontal cortexshowed relatively more activation by the pleasant than the neutral touch, relative to the somatosensory cortex.

ConclusionsStrong activation of the lateral orbitofrontal cortex was produced by pleasant tactile stimuli. There was statisticallysignificantly relatively more activation in the lateral orbitofrontal cortex than in the primary somatosensory cortexby the pleasant than by the neutral stimuli. This result provides evidence for the first time that affectively positiveaspects of touch are represented in the orbitofrontal cortex. In addition, the results also show that potentially it ispossible to measure what could be implicit (unconscious) affective responses to stimuli by the use of tMR!.

ReferencesI. Kaas, JH Anat. Anz. 1995, 175: 509-518.2. Morecraft, RJ et al 1992 J. Compo Neurol. 1992,323: 341-358.3. Rolls, ET et al 1989 Eur. J. Neuroscience 1: 53-60.4. Rolls, ET Phil. Trans. Roy. Soc. B 1996,351: 1333-1344.5. Mansfield, P et al 1994, JCAT, 18: 339-343.6. Zatorre, RJ et al, 1992 Nature, 360: 339-340.

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ORAL SESSIONS: MOTOR AND SENSORY

Microstructure and Function of the Primary Somatosensory Cortex of Man.An Integrative Study Using Cytoarchitectonic Mapping and PET

S. Geyerl, A. Ledberg2, T. Schormannl, K. Zilles1, P.E. Roland2

1Brain Research Institute, Heinrich Heine University, DUsseldorf, Germany.2Div. Human Brain Research, Dept. Neuroscience, Karolinska Institute, Stockholm, Sweden.

Modem imaging techniques, e.g. PET or tMRI, locate foci of cortical activity with increasing spatial resolution.These foci, however, have so far been related to macrostructural landmarks of the cerebral cortex (i.e. gyri andsulci) only. There is evidence in primates that cortical areas as functional entities can be defined as to theirlocation and extent ~ microstructurally. Macrostructural landmarks, however, usually do not matchmicrostructurally defined inter-areal borders. For this reason, (macrojstructural-functional correlations have beenproblematic. In a new approach, we have matched functional imaging data with microstructurally defined corticalareas (1). In the present study, we examine the functional activation of a priori microstructurally definedsomatosensory areas 3a, 3b, 1&2.

Tissue Matertal, Suhjects and MethodsT1 weighted MRI scans (l.5T system: FLASH technique) were obtained from 5 formalin fixed postmortembrains. The brains were then embedded in paraffin, sectioned as a whole in the coronal plane (section thickness20,.nn), and cell stained. Areas 3a. 3b and 1&2 were delineated cytoarchitectonically in these sections.Histological artifacts due to tissue processing, e.g. shrinkage, were eliminated by linear and non-linear alignmentprocedures using the MR volume of the identical brain as anatomical reference (2). The location and extent of thecytoarchitectural areas were transformed into standard anatomical space en. The presumed somatosensory fingerregions (4) of areas 3a, 3b and 1&2 were pre-defined as volumes of interest (VOl's). Each VOl representing thespace in which the cytoarchitectural area of three or more out of the five brains overlapped.

The functional activation of somatosensory areas W~L'" tested in 2D paradigms, one passive and one active. In thepassive stimulation, seven subjects were stimulated with curvature, edge and roughness stimuli on the index fingerand discriminated these shape primitives. In the active paradigm, eight other subjects tactually discriminated theshape of rectangular parallelepipda (5). For both groups, rest was the control condition. The blood flow wasmeasured with I 50-butanol and PET. Co-registered MR scans were used as anatomical reference and functionaldata were transformed into standard anatomical space (3).

ResultsThe passive somatosensory stimulation did not activate area 3a. Area 3b was moderately but significantlyactivated by edge, curvature and roughness discrimination. Area 1 & 2 was more strongly activated by the threepassive discrimination tasks. In addition. active discrimination of shape activated areas 3b and 1&2, but not area3a.

ConclusionsBoth areas 3h and 1&2 are significantly activated no matter whether shape primitives or shape was discriminatedpassively or actively. As area 3a is assumed to receive information from muscle spindles and tendons mainly, suchsensory feed-back seemed to he less important in active discrimination of shape. Further, somatosensorymechanoreceptor stimulation activated areas 3h and 1&2, but not area 3a.

References1. Geyer, S. et al. Nature 1996,382: 805-807.2. Schormann, T. et aI. IEEE Trans. Met!. Imaging 1995, 14: 25-35.3. Roland, PE. etal. Human Brain Mapping 1994, 1: 173-184.4. Rolmld, PE. Brain Res. Rev. 1987, 12: 43-94.5. Roland, PE., and Mortensen E. Brain Res. Rev. 1987, 12: 1-42.

Supported by grams hom the DFG (SFB 194/A6), BioMed 2, and Bio'Tech.

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Cerebellar and Cortical Magnetic Fields to Omission of SomatosensoryStimuli in Normal Human Subjects

C. D. Tesche! and J. Karhu1,2

l Low Temperature Laboratory, Helsinki University of Technology, Espoo 02150, Finland2 Kuopio University Hospital, Kuopio 70211, Finland

The cerebellum has been considered for decades as a motor organ which adjusts and improves motor performance(1). Contrary to the early clinical findings describing negligible sensory impairment after cerebellar lesions, it hasbeen shown that the main output relay, the dentate nucleus activates strongly during processing of sensory data (2),and we have reported very recently for the first time short-latency somatosensory evoked magnetic fields fromsources in the human cerebellum (3). Recent studies have also demonstrated a strong cognitive role for thecerebellum for example in the judgement of time intervals. In this study, we evaluated the pattern of activityelicited by random omission of somatosensory stimuli. Our aim was to find features of neurophysiological activitywhich may characterize sensory and timing functions of cerebellum.Subjects and methodsData were recorded with a whole-head 122-channel MEG system (4) from four healthy right-handed adults whoprovided informed consent. Unilateral median nerve stimulation was delivered through transcutaneous electrodesat the wrist. Constant current pulses (0.3 ms duration) at interstimulus intervals of 0.5 s were randomly interspersedwith missing stimuli (15% omission). Data were bandpass filtered at 0.03 - 330 Hz and sampled at 1 kHz. Avertical electro-oculogram was used to identify and reject data contaminated by eye movements and blinks.Neuromagnetic responses were averaged time-locked to the median nerve stimulation and to the omission.Equivalent current dipole locations and orientations were determined for sources in sensorimotor cortex from aleast-squares fit to the data. A priori physiological information was then incorporated into the analysis of the MEGdataAnatomical features of individual subject's brainstem, thalamus and cerebellum obtained from individualmagnetic resonance (MR) images were used to constrain source areas for postsynaptic activity following nervestimulation. Cranial volumes obtained from the same images were utilized in the construction of a realistic headmodel for each subject for the forward modelling of magnetic field patterns from test sources in each area. Signal­space projection (SSP) (5) was then used to identify responses consistent with neuronal population activity in cere­bellum. Finally, SSP waveforms reflecting activation of cortical sensorimotor areas and cerebellum were digitallyfiltered at 3-8, 8-12, 15-25,25-35,35-45,40-60,60-80, 100-200, and 200-300Hz to compare the cortical andcerebellar patterns of activation with respect to the oscillatory content.ResultsAll four subjects showed normal, contralaterally dominant, highly localized somatosensory evoked magnetic fields(SEFs) at 20-60 ms after left and right median nerve stimulation. Widespread field patterns characterized responsesto omittedstimuli. At 100-200 ms right hemisphere responses were larger than left, independent of which hand wasstimulated. The oscillatory content of responses time-locked both to actual stimuli and to the omissions showed aconsistent pattern in all subjects. The SSP waveforms characterizing cerebellar activation showed most prominentactivity at 3-8 Hz and 8-12 Hz following both stimuli and omissions. In contrast, cerebellar responses at 25-45 Hzwere more prominent following stimuli than following omissions. Cortical SSP waveforms also showed phase­locked activity at 3-45 Hz with additional responses at 60-300 Hz.ConclusionsThe neurophysiological activity of both cortical and cerebellar source areas were characterized with good temporalresolution utilizing whole-head MEG system and SSP analysis. Cerebellar SSP waveforms were not identical tocortical responses. These data support not only separate processing of somatosensory stimuli (3), but also of omis­sions in both cerebellar and cortical somatosensory areas.

This study was supported by a grant from NIH (NINDS grant lROl NS34533-01Al).

References1. Holmes, G. Brain. 1939,62: 1-30.2. Gao, J.-H., Parsons L., Bower J., Xiong J., Li J., Fox P. Science. 1996,272: 545-547.3. Tesche, CD., Karhu, J. Brain Res. 1997, 744: 23-31.4. Ahonen, A.I., Hamalainen, M., Kajola, M:, Lounasmaa, 0., Simola, J., Tesche, C; Vilkman, V. Proceedings ofthe Satellite Symposium on Neuroscience and Technology, 14th Annual International Conference of the IEEEEngineering in Medicine and Biology Society. 1992,16-20.5. Tesche, CD., Uusitalo, MA., Ilmoniemi, RJ., Huotilainen, M., Kajola, M., Salonen, O. Electroenceph. Clin.Neuropbysiol. 1995,95: 189-200.

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Different activation patterns in the occipital cortex of late andcongenitally blind subjects

C. Biichel, C. J. Price, R. S. J. Frackowiak and K. J. Friston

Wellcome Department ofCognitive Neurology, Institute ofNeurology, London, UK

(A) Significant differences in activations engendered by Braille readingbetween the late and congenitally-blind group. (B) Plot of activity at themost sig nifica nt voxe l in the primary visual cortex.

LB1cblindCongennally

1 2 3 4

Bra ille Audnory Brail le Auditory

78

76

90

s BB~0 86e~~ 84

~~ BZ...l;! BO

Adjusted rCBF for vOllel X: 2mm. V: - 86m m . Z: - 4m m

92

sag tal

A key issue in developmental neuroscience is the role of activity-dependent mechanisms in the epigenetic inductionof functional organisation in visual cortex. Ocular blindness and ensuing visual deprivation is one of the raremodels available for the investigation of experience dependent cortical reorganisation in man.

Six male (mean age 49.2±12), congenitally blind and three late blind (mean age of onset of blindness 18.3±3.8;mean age 45±7.6) proficient Braille readers were studied with Hz'sO PET comparing Braille reading and auditoryprocessing. During 6 of 12 scanning sessions we presented words and non-words (consonant letter strings) every2.5 s. During the remaining 6 scans subjects listened to words and reversed words. All conditions involved a featuredecision task and incidental word processing. The targets were (i) a right lower dot in Braille stimuli and (ii) a tonepresented immediately after some auditory stimuli. Statistical analysis was performed with SPM96

In the congenitally blind group Braille stimuli, in contrast to auditory stimuli, activated a parieto-occipital systemincluding bilateral parietal association areas (BA 7), superior visual association cortex (superior BA 19) and thecerebellum. Additional activations in the left hemisphere were found in primary sensory cortex, parietal BA 40,inferior visual association cortex (inferior BA 19) and the occipito-temporal junction. Subjects who had lost theirsight after puberty showed a similar pattern of activation with a striking difference. In the late blind group therewas an activation in primary visual cortex, which was missing in congenitally blind subjects.

A direct comparison of the differences in Braille-specific activations between the late and congenitally-blind groupsshowed a statistically significant group by condition interaction in the primary visual cortices and the right medialoccipital cortex (Figure IA). A plot of regional cerebral blood flow (rCBF) in VI shows higher values duringBraille reading in the late-blind group than in auditory processing for both blind groups and Braille reading in thecongenitally blind group (Figure IB). This finding suggests that the differential effect is due to increased rCBFduring Braille reading in the late blind subjects as opposed to decreases in rCBF during all other conditions.

A B The distinction between late andcongenitally blind subjects isconsistent with predictions fromprimate studies: Early visualdeprivation in lid-sutured monkeysresults in crossmodal re-organisationof prestriate areas. After a year ofvisual deprivation 20% of cellsstudied in area 19 respondedexclusively to tactile stimuli. Cellsin the centre of area 17 showed noresponse to tactile stimuli, though afew neurons at the border betweenarea 17 and 18 responded weakly totactile stimulation (1).

We therefore conclude thatdifferential activation of prestriatevisual areas during Braille reading,relative to auditory processing,supports task-specific cross-modalresponses in prestriate cortex. Inlate-blind subjects, it cannot be

excluded that reciprocal interactions associated with mental imagery mediate activation in the primary visual cortex.The demonstration that VI activation depends on the onset of blindness is in contrast to another study (2), thatattributes V I activation to the reorganisation of primary visual cortex to accept non-visual sensorimotorinformation, possibly for further processing.

References

I. Hyvarinen J., Carlson S., Hyvarinen L. Neurosci Lett 1981,26: 239-43

2. Sadato N., Pascual-Leone A., Grafman J., Ibanez V., Deiber M.-P., Dold G., Hallett M. Nature 1996 380: 526­528

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