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Rostral Fastigial Nucleus Activity in the Alert Monkey During ThreeDimensional Passive Head Movements C. SIEBOLD, L. GLONTI, S. GLASAUER, AND U. BÜTTNER Department of Neurology and Center for Sensorimotor Research, Ludwig Maximilians University, D 81377 Munich, Germany Siebold, C., L. Glonti, S. Glasauer, and U. Büttner. Rostral fastigial nucleus activity in the alert monkey during three-dimensional passive head movements. J. Neurophysiol. 77: 1432–1446, 1997. The fastigial nucleus (FN) receives vestibular information predominantly from Purkinje cells of the vermis. FN in the monkey can be divided in a rostral part, related to spinal mechanisms, and a caudal part with oculomotor functions. To understand the role of FN during movements in space, single-unit activity in alert monkeys was recorded during passive three-dimensional head movements from rostral FN. Seated monkeys were rotated sinusoidally around a horizontal earth-fixed axis (vertical stimulation) at different orientations 157 apart (including roll, pitch, vertical canal plane and intermediate planes). In addition, sinusoidal rotations around an earth-vertical axis (yaw stimulus) included different roll and pitch positions ( {107, {207 ). The latter positions were also used for static stimulation. One hundred fifty-eight neurons in two monkeys were modulated during the sinusoidal vertical search stimulation. The vast majority showed a uniform response pattern: a maximum at a specific head orientation (response vector orientation) and a null response 907 apart. Detailed analysis was obtained from 111 neurons. On the basis of their phase relation during dynamic stimulation and their response to static tilt, these neurons were classified as vertical semicircular canal related (n Å 79, 71.2%) or otolith related (n Å 25; 22.5%). Only seven neurons did not follow the usual response pattern and were classified as complex neurons. For the vertical canal-related neurons (n Å 79) all eight major response vector orientations (ipsilateral or contralateral anterior canal, posterior canal, roll, and nose-down and noseup pitch) were found in FN on one side. Neurons with ipsilateral orientations were more numerous and on average more sensitive than those with contralateral orientations. Twenty-eight percent of the vertical canal-related neurons also responded to horizontal canal stimulation. None of the vertical canal-related neurons responded to static tilt. Otolith-related neurons (n Å 25) had a phase relation close to head position and were considerably less numerous than canal-related neurons. Except for pitch, all other response vector orientations were found. Seventy percent of these neurons responding during dynamic stimulation also responded during static tilt. The sensitivity during dynamic stimulation was always higher than during static stimulation. Sixty-one percent of the otolith-related neurons responded also to horizontal canal stimulation. These results show that in FN, robust vestibular signals are abundant. Canal-related responses are much more common than otolithrelated responses. Although for many canal neurons the responses can be related to single canal planes, convergence between vertical canals but also with horizontal canals is common. INTRODUCTION The cerebellum plays a major role in the processing of vestibular signals. This does not only apply to the vestibu1432 locerebellum (flocculus, nodulus) but also to the vermis. The vermis receives a major mossy fiber input from the vestibular nuclei (Kotchabhakdi and Walberg 1978). The Purkinje cells (P cells, the only output element of the cerebellar cortex) of the vermis project to the fastigial nucleus (FN), the most medial deep cerebellar nucleus (Armstrong and Schild 1978), and also directly to the vestibular nuclei (Yamada and Noda 1987). The anterior vermis (lobules I–V) is considered to be part of the spinocerebellum. In contrast, lobuli VI and VII of the posterior vermis receive a major pontine input (Yamada and Noda 1987) and are classified accordingly as pontocerebellum. These anatomic divisions are also reflected in functional differences. Whereas the anterior vermis is involved in spinal mechanisms (posture, neck, gait), lobuli VI and VII of the posterior vermis play a role in oculomotor functions (oculomotor vermis, Yamada and Noda 1987). The P cells of the vermis project onto the ipsilateral FN in a topographic fashion, i.e., the anterior vermis to the rostral FN and the posterior vermis to the caudal FN (Armstrong and Schild 1978). Accordingly, a functional division can also be demonstrated for FN by single-unit recordings under natural conditions. Whereas eye movement (saccade, smooth pursuit)-related neurons are encountered in the caudal FN (Büttner et al. 1991; Fuchs et al. 1993), neurons in rostral FN exhibit no activity related to individual eye movements, but respond to vestibular stimulation (Büttner et al. 1991; Gardner and Fuchs 1975). Most studies of the vestibular signals in FN have concentrated on stimulation in the horizontal plane around the Zaxis (yaw stimulation). Under these conditions the majority of neurons in rostral FN exhibit a type II response (Büttner et al. 1991; Gardner and Fuchs 1975) according to the nomenclature of Duensing and Schaefer (1958). These neurons have no eye movement sensitivity and are classified as ‘‘vestibular-only’’ neurons. Neurons in caudal FN with vestibular sensitivities generally also respond during smooth pursuit eye movements, many of them encoding ‘‘gaze velocity’’ with little or no response during the vestibuloocular reflex and an increased response during visual suppression of the VOR (Büttner et al. 1991). Under natural conditions, head movements are performed in three-dimensional space and vestibular signals are generated accordingly. Very little is known about the central processing of three-dimensional vestibular signals beyond the vestibular nuclei. Gardner and Fuchs (1975) reported that a high percentage (75%) of vestibular-only neurons in rostral 0022-3077/97 $5.00 Copyright q 1997 The American Physiological Society / 9k0e$$mr20 J523-6 09-02-97 13:54:50 neupa LP-Neurophys FASTIGIAL ACTIVITY IN 3D HEAD MOVEMENTS 1433 FIG . 1. Schematic drawing of the applied stimuli. Drawing of the monkey’s head includes ( A) approximate orientation of the vertical canals and (B) and (C) approximate orientation of the horizontal canals. A: head orientations during vertical dynamic stimulation. RALP, right anterior/left posterior; LARP, left anterior/right posterior. B and C: head orientations for the static positions, which were also used in combination with yaw stimulation around the Z-axis. RED, right ear down; LED, left ear down; NU, nose up; ND, nose down. During yaw stimulation with ND the horizontal canal is close to the optimal stimulation plane. FN were modulated during horizontal and pitch stimulation, indicating some canal convergence. More systematic studies have been performed in the vestibular nuclei. In the alert cat it was found that most neurons received input from one canal pair. Neurons with input from two canal pairs were more common than those with input from all three canal pairs (Baker et al. 1984a). About one third of the neurons had more complex response properties and differed in their spatial orientation and dynamic properties (spatial-temporal convergence) from canal responsive neurons, indicating canal-otolith interaction (Baker et al. 1984a,b). The detailed studies from vestibular nerve afferents have classified vertical canal plane (VCP) responsive neurons (Goldberg and Fernandez 1984). According to this, the left anterior and right posterior (LARP) canals lie in almost the same plane of orientation, as do the right anterior and left posterior (RALP) canals. Optimal activation occurs when the nasooccipital axis is in the LARP or RALP plane ( b Å 0457 and /457, respectively) during stimulation around an earth-horizontal axis (Fig. 1A). For the horizontal canal (HC) pair, the optimal orientation during yaw stimulation around the Z-axis in the monkey is during nose-down tilt of g Å 157 (Fig. 1C) (Böhmer et al. 1985). With increasing deviations from the optimal orientation the response declines monotonically with a sine function to zero (null response) when the canal plane is orthogonal to the optimal orientation. The phase of the neuronal response is constant, and is close to stimulus velocity except for a 1807 phase shift at the null response. This applies for stimulus frequencies between 0.1 and 2 Hz. All other neuronal response characteristics (constant responses and varying phases at different orientations) indicate spatiotemporal convergence with an (additional) otolith input, as has been described for the vestibular nuclei (Baker et al. 1984b). / 9k0e$$mr20 J523-6 To fully understand the role of the cerebellum in the control of three-dimensional head-dependent movements and other movements it is necessary to know what vestibular information is present. Because detailed information on the response pattern of rostral FN neurons during yaw stimulation is already available in the literature (Büttner et al. 1991; Gardner and Fuchs 1975), we focused our investigation on neuronal activity to natural vestibular stimulation in pitch, roll, and intermediate planes, applying a pure vertical searching stimulus (pitch, roll, or VCP stimulation). In addition, most neurons that responded to vertical dynamic stimulation were tested subsequently for horizontal modulation. It will be shown that many FN neurons carry a clear vestibular signal, which can be related to individual canals. Many neurons also show a convergence either of different vertical canals (VCs) or of HCs and VCs. Other neurons had an otolith input. Only vestibular-only neurons will be considered. Preliminary data have been reported elsewhere (Büttner et al. 1996). METHODS Two monkeys (Macaca mulatta) were used for this study. Before surgery the monkeys were accustomed to sitting in a primate chair and were trained to follow a small visual target (0.57 ) with the eyes. Under general anesthesia and aseptic conditions, the monkeys were chronically prepared for single-unit recordings (for details see Boyle et al. 1985). In short, a recording chamber was implanted (stereotaxic coordinates: mediolateral 0 mm, posterior 6 mm) to allow a vertical approach in the stereotaxic plane of FN on both sides. Horizontal, vertical, and torsional eye position was recorded by a dual search coil system (Bartl et al. 1996) and neuronal activity was recorded with varnished tungsten microelectrodes (impedance 2.5–4 MV ). During the experiment the head was immobilized by a head holder and the monkey sat with the head erect (stereotaxic horizontal) in a primate chair. 09-02-97 13:54:50 neupa LP-Neurophys 1434 C. SIEBOLD, L. GLONTI, S. GLASAUER, AND U. BÜTTNER Definitions of coordinates and directions The directions of the head-fixed coordinate system are defined according to the right hand rule, with positive values for leftward movements around the Z-axis (yaw), downward movements around the Y-axis (pitch), and right-ear-down movements around the X-axis (roll). The attributes pitch/roll/yaw are used to indicate head-fixed coordinates throughout the paper. Throughout the manuscript we distinguish between VCP-related neurons, with the best response during LARP and RALP stimulation, and VC-related neurons, which includes also pitch and roll neurons. The stimuli and the position of the monkey are described relative to an earth-fixed coordinate system to indicate whether or not the monkey was rotated around an axis parallel to gravity (earth-vertical axis rotation, no stimulation of the otoliths). Vestibular stimulation The primate chair was mounted on a rotating device with three motor-driven axes of rotation. The innermost frame allowed rotations around the monkey’s Z-axis [angle b, used to rotate the monkey to predefined positions (range {907, step size Db Å 157 )] (Fig. 1). The medium frame rotated the primate chair around an earth-horizontal axis (angle d, dynamic and static vertical stimulation). The outermost frame rotated the whole device around an earth-vertical axis (angle d, dynamic horizontal stimulation). Three different dynamic stimulation paradigms were applied (Fig. 1). 1) VC stimulation with earth-horizontal axis rotation in different b positions. Sinusoidal rotations around the earth-horizontal axis (angle d, referred to as ‘‘vertical stimulation’’ throughout the paper) caused pitch or roll stimulation of the monkey, depending on the orientation of the inner frame (angle b, pitch: b Å 07, roll: b Å {907 ) (Fig. 1). Thus pitch stimulation occurred around the Y-axis and roll stimulation around the X-axis in the monkey’s head coordinates. With orientations of the primate chair of b Å {457, stimulation was close to the LARP or RALP VCP orientation, respectively. As a routine, orientations were investigated at Db Å 157 intervals, and the stimulus amplitude was g Å {157 at 0.6 Hz (maximum velocity {607 /s). This yielded 12 orientations (13 including b Å /907 and b Å 0907, Fig. 1A). 2) Earth-vertical axis rotation in different roll positions ( b Å {907 ). Similarly, sinusoidal rotations around the earth-vertical axis were applied with an amplitude d Å {157 at 0.6 Hz while the monkey remained in different roll positions by adjusting the medium frame to different fixed roll angles ranging from g Å 0207 to g Å 207 ( Dg Å 107 ) (Fig. 1B). 3) Earth-vertical axis rotation in different pitch positions ( b Å 07 ). Sinusoidal rotations around the earth-vertical axis were applied with an amplitude d Å {157 at 0.6 Hz while the monkey remained in different pitch positions by adjusting the medium frame to different fixed pitch angles ranging from g Å 0207 to g Å 207 ( Dg Å 107 ) (Fig. 1C). Amplitudes of sinusoidal stimulation could be varied between 0 and {207. Static tilts up to g Å {207 were applied in different orientations of the inner frame (angle b ). Data analysis All signals (3-dimensional head and eye position, neuronal activity) were monitored and stored on an FM tape recorder (Teac XR 310) for further off-line computer analysis. Signals were digitized with real time occurrence of neuronal activity (spikes) and a sampling rate of 200 Hz for the other channels. For a given sinusoidal stimulus condition, neuronal activity was averaged for 7–12 cycles. Averaged neuronal activity was fitted by a least-square best-sine function. In cases in which the neuronal activity was silenced during sinusoidal stimulation (‘‘cutoff ’’), a weighting factor W (W Å / 9k0e$$mr20 J523-6 1 for the episode with neuronal activity and W Å 0 for the cutoff) was applied. Thus, assuming that the modulation of the neuronal activity had the same frequency as the sinusoidal vestibular stimulation, the least-square best-sine function was defined by the neuronal activity above threshold. Sensitivity (imprs 01 /(degrs 01 ), i.e., the amplitude of the resulting leastsquare best-sine function divided by the velocity of the vestibular stimulation) and phase were determined in relation to head velocity, with positive phase values indicating that neuronal activity was leading head velocity. Neurons were grouped in one of four major orientation groups [pitch ( b Å 07 ), roll ( b Å {907 ), RALP, and LARP ( b Å {457 )] that lay closest ( Db Å {22.57 ) to their direction of maximum modulation. Because maximal responses can be related to each of the two stimulus directions (up or down), eight response types were distinguished. Response always refers to excitation in a given stimulus direction. During static tilt stimulation, neuronal activity was sampled over 40–60 s and a neuron was considered as modulated if the firing frequencies in two positions were statistically different (t-test, P õ 0.001). At the end of all experiments, the animal was placed under deep barbiturate anesthesia and perfused transcardially with 10% Formalin. Coronal sections, taken every 50 mm in the stereotaxic plane, were stained with cresyl violet. Electrode tracks were reconstructed with the aid of small electrolytic lesions that had been placed by passing 30- to 100-mA current for 10–20 s after particularly fruitful recording sessions. RESULTS General characteristics The results are based on the quantitative analysis of 158 neurons responding to dynamic VC stimulation, and according to histological reconstructions located in FN. From these 158 neurons, 120 were also tested during yaw stimulation and 61 during static tilt. For 53 neurons, all three conditions (dynamic vertical and horizontal stimulation as well as static tilt) were applied. Neurons responding to dynamic vertical stimulation composed Ç15–20% of the neurons tested. Some of these nonresponsive neurons localized in the caudal FN were clearly modulated with saccades (Büttner et al. 1991; Fuchs et al. 1993) and will not be considered here. Neurons with both vestibular and smooth pursuit sensitivities will also not be considered. All vestibular-only neurons (n Å 158) were spontaneously active (range 21–104 imp/s; average 58.5 imp/s) with an irregular discharge rate. Coefficient of variation of the interspike interval for all neurons ranged between 0.2 and 1.4, with an average of 0.73 (see Fig. 7), which is considerably higher than the values found for vestibular nerve afferents. No attempt was made to relate occasional bursts or silent periods in some of the neurons to a certain behavioral pattern. None of the vestibular-only neurons had activity related to saccades or eye position. Vestibular responses were the same in light and darkness. Responses were also not affected by the level of alertness as judged by the eye movement recordings. The disappearance of the vestibular modulation for several cycles (waxing and waning), which has been described for vestibular responses of PCs in the oculomotor vermis (Suzuki and Keller 1988a,b), was seen in three (2%) neurons. Because it was not a common phenomenon it will not be considered further. During sinusoidal vestibular stimulation many neurons were silenced in one direction (cutoff) as shown in Fig. 2. 09-02-97 13:54:50 neupa LP-Neurophys FASTIGIAL ACTIVITY IN 3D HEAD MOVEMENTS 1435 FIG . 2. Activity of a ‘‘vestibular-only’’ neuron in the right fastigial nucleus (FN) during sinusoidal vertical stimulation (0.6 Hz, {607 /s) around a horizontal earth-fixed axis with the head oriented in the directions yielding maximal ( b Å 0307 ) and minimal ( b Å 607 ) response modulation. Shown are individual impulses, instantaneous frequency, and stimulus velocity. Orientations for minimal (null) and maximal responses are 907 apart. During maximal responses neuronal activity is in phase with stimulus velocity and decreases to 0 during part of the cycle (‘‘cutoff ’’). Because this neuron had its best modulation during upward head movements with the head oriented at 0307 (ipsilateral to the recording side), it was classified as an ipsilateral posterior canal (iPC) neuron. With our stimuli this was found in 51% of the neurons, which is in agreement with earlier studies showing that cutoff is a common phenomenon (Büttner et al. 1991; Gardner and Fuchs 1975). All neurons showing an activity increase during stimulation in one direction showed a decrease in the opposite direction (types I and II). None of the neurons showed an activity increase (type III) or decrease (type IV) in both directions. Of 158 neurons, 47 were only tested in fewer than four different orientations during dynamic vertical stimulation. These data were considered insufficient to permit conclusions about the response vector orientation, and particularly about complex response patterns (see below). They were therefore excluded from further analysis and not included in Tables 1 and 2. However, the data supported the general finding that the activity of most neurons (32 of 47) was in phase ( {457 ) with head velocity and that for only 15 of 47 neurons was the activity in phase ( {457 ) with head position. Of 28 neurons tested, 12 exhibited an additional response to HC (yaw) stimulation. The responses of seven of these neurons were type I and the remaining five were type II responses (Duensing and Schaefer 1958). The remaining 111 neurons were attributed to one of the / 9k0e$$mr20 J523-6 following groups according to their dynamic response during VC stimulation and their phase relation: VCP and VC convergence neurons (n Å 79), otolith-related neurons (n Å 25), and complex neurons (n Å 7). Because we determined response vector orientations at one frequency, we cannot exclude the possibility that some of the neurons classified as VC related reflect an irregular otolith input. In contrast to regular otolith neurons, for which the phase stays close to head position, the phase for irregular neurons can vary considerably ( ú1807 ) for frequencies ú0.01 Hz (Schor et al. 1985). We assumed a VC response when the phase was within {457 of head velocity and neurons did not respond to static tilt. VC and VC convergence neurons Seventy-nine neurons were attributed to this group. Of these, 59 were tested at all 12 orientations (13, including roll b Å /907 and 0907 ) during vertical dynamic stimulation. The remaining 20 neurons were investigated at 4–11 orientations, which covered a range of ¢1207 for each neuron. Of the 79 neurons, 53 were classified as VCP-related neurons with an optimal response GENERAL CHARACTERISTICS. 09-02-97 13:54:50 neupa LP-Neurophys 1436 TABLE C. SIEBOLD, L. GLONTI, S. GLASAUER, AND U. BÜTTNER 1. Sensitivity and phase relation of vertical canal-related neurons Sensitivity, (imprs01 )/(degrs01 ) iR cR uP dP iAC cAC iPC cPC Ipsi Contra Total Phase (Relative to Head Velocity) N Average Range Average Range 10 6 3 7 21 3 21 8 52 17 79 0.82 0.5 0.66 0.89 0.63 0.54 1.25 0.71 0.88 0.6 0.8 0.22–1.60 0.34–0.80 0.36–0.88 0.35–1.60 0.33–1.25 0.43–0.70 0.42–2.52 0.36–0.94 0.22–2.52 0.34–0.94 0.22–2.52 3.5 04.6 14.75 4.5 3.1 011.5 4.4 06.5 3.6 06.5 2.07 /25 to 018 /29 to 021 /22 to /7.5 /20 to 05 /22 to 020 05 to 018 /20 to 026 /0.6 to 019 /29 to 026 /29 to 021 /29 to 026 0.59 0.39 0.49 0.23–1.24 0.30–0.61 0.23–1.24 6.1 26.8 16.4 /44 to 045 /50 to /1 /50 to 045 Horizontal canal stimulation Type 1 Type 2 Total 10 9 19 Ipsi and Contra: combined values for neurons with a response vector orientation ipsilateral [ipsilateral roll (iR), ipsilateral anterior canal (iAc), ipsilateral posterior canal (iPC)], and contralateral [contralateral roll (cR), contralateral anterior canal (cAC), contralateral posterior canal (cPC)] to the recording side. The values for some of the vertical canal-related neurons also responding to horizontal canal stimulation are shown at bottom. uP, pitch up; dP, pitch down. during ipsilateral anterior canal (iAC), ipsilateral posterior canal (iPC), contralateral anterior canal (cAC), or contralateral posterior canal (cPC) stimulation (Table 1). The other 26 neurons reflected convergence of two VCs with optimal responses during either roll or pitch movements. Of the 79 neurons investigated during dynamic vertical stimulation, 69 were also tested during HC stimulation around the earthvertical axis. All neurons had a maximal response for one orientation during vertical dynamic stimulation and a minimal (null) response with spontaneous activity only at an orientation 907 apart (Figs. 2 and 3). Between maximum and minimum the responses decreased monotonically and were closely fit by a sine function (Fig. 3). Phases of the neuronal response were for all orientations on average close to stimulus (head) velocity, except for a phase shift of 1807 around the minimal (null) response. TABLE 2. Phases ranged for different neurons between /297 (lead) and 0267 (lag). Phases for neurons with different optimal orientations were similar (Table 1). None of the neurons tested in this group (n Å 41) responded to static tilt in the roll, pitch, or optimal angle b orientation. This supports the assumption that these neurons receive only a canal and not an otolith-related input. STATIC TILT. In each FN on both sides all eight response types [iAC, cAC, iPC, cPC, ipsilateral roll (iR), contralateral roll (cR), pitch down (dP), and pitch up (uP)] were found (Table 1). Thus neurons had their optimal response in the canal planes (Fig. 3A), but also during iR, cR, uP, and dP movements (Fig. 3B). In the optimal orientation the sensitivity at 0.6 Hz varied for different neurons between 0.22 and 2.52 (imprs 01 )/(degrs 01 ). There was no statistically significant difference between the RESPONSE VECTOR ORIENTATION. Sensitivity and phase relation of otolith-related neurons Sensitivity, (imprs 01 )/(degrs01 ) iR cR i45 ND c45 ND i457 NU c457 NU Total Phase (Relative to Head Velocity) N Average Range Average 5 5 7 4 1 4 25 0.62 0.52 0.69 0.81 0.7 0.57 0.62 0.51–0.85 0.27–0.72 0.34–0.97 0.7–0.96 0.7 0.30–0.93 0.27–0.97 076.2 093.5 077 0100.6 081 083.2 084.9 0.67 0.63 0.66 0.54–0.78 0.63 0.54–0.78 29.8 42 31.5 Range 060 062 069 063 081 074 060 to to to to 0133 0111 0128 0110 to 0106 to 0133 Horizontal canal stimulation Type 1 Type 2 Total 10 1 11 /54 to 026 42 /54 to 026 Values were measured during dynamic vertical stimulation (top) and during dynamic horizontal stimulation (bottom) ipsilateral (i), contralateral (c), nose down (ND), nose up (NU). For abbreviations, see Table 1. / 9k0e$$mr20 J523-6 09-02-97 13:54:50 neupa LP-Neurophys FASTIGIAL ACTIVITY IN 3D HEAD MOVEMENTS 1437 FIG . 3. Sensitivity (top) and phase (bottom) of an iPC neuron (A) and a pitch down (dP) neuron ( B) during different head orientations at sinusoidal vertical stimulation (0.6 Hz, {607 /s). Sensitivity decreases monotonically from a maximal to a minimal value at an orientation 907 apart. Dashed line: fit by a sine function (note that negative values of the sine function were multiplied by 01). The calculated maxima are b Å 0467 for A and b Å 037 for B. Neuronal activity increases during up (A) and down (B) head movements. Phase is close to head velocity, with a slight phase lag in A, except for a phase shift of 1807 around the null response (457 in A and {907 in B). sensitivity for different response types except for iPC neurons, which yielded the most sensitive neurons. There was no difference of sensitivities between roll-, pitch-, and canalrelated neurons. However, neurons with ipsilateral orientations (iAC, iPC, iR) were on average (sensitivity 0.88 (imprs 01 )/(degrs01 ) more sensitive than contralateral orientations (cAC, cPC, cR) (average sensitivity 0.6 (imprs 01 )/(degrs01 ) (Fig. 4A). These differences were statistically significant (P õ 0.001, t-test for independent samples). This was also reflected in individual neurons. The largest sensitivity for a neuron with a contralateral optimal orientation was 0.94. However, there were 18 neurons with sensitivities between 0.9 and 2.52 (imprs 01 )/(degrs01 ) and ipsilateral orientations. Furthermore, 52 neurons (75%) had an ipsilateral canal (iAC, iPC, iR)-related orientation compared with 17 (25%) neurons related to contralateral orientation (cAC, cPC, cR) (Fig. 4A). There was a definite number of pitch neurons (n Å 10), which increased their activity with nose-down (dP neurons) or nose-up (uP neurons) movements (Fig. 3B). Accordingly they had null responses during roll movements. HC STIMULATION. The majority of neurons tested did not respond during yaw stimulation ( g Å 07 ) (45 of 69, 65%) on the basis of a sensitivity criterion of ú0.2 / 9k0e$$mr20 J523-6 (imprs 01 )/(degrs01 ). However, 24 neurons were modulated, 14 neurons with a type I and 10 neurons with a type II response. Of the 24 yaw-modulated neurons, 5 were roll neurons, 1 was a pitch neuron, and the remaining 18 were VCP-related neurons. As shown by the following numbers, there was no specific preference for any combination between horizontal and vertical response types: type II / iAC (n Å 4), type II / cAC (n Å 1), type II / iPC (n Å 3), type II / cR (n Å 2); type I / iAC (n Å 3), type I / iPC (n Å 6), type I / cPC (n Å 1), type I / iR (n Å 2), type I / cR (n Å 1), type I / dP (n Å 1). Yaw stimulation was routinely applied with the monkey’s head in the erect position, which is Ç157 off the optimal orientation for the HCs (Fig. 1C) and leads to a VC stimulation (Böhmer et al. 1985). The effect of the angle between the VC orientation and the stimulus plane (defined by g ) during yaw stimulation applies for VCP-related and roll neurons, but not for pitch neurons. It follows simple trigonometric rules (see APPENDIX ). The maximal (100%) VCP response is therefore reduced to Ç20% at g Å 07 ( b Å 07 ) and to 0% at g Å /157. For roll neurons this value would be 27% at g Å 07. This implies a sensitivity of ¢1.0 (imprs 01 )/(degrs01 ) for VCPrelated neurons and 0.8 (imprs 01 )/(degrs01 ) for roll-related neurons during earth-horizontal axis rotation to result in a mod- 09-02-97 13:54:50 neupa LP-Neurophys 1438 C. SIEBOLD, L. GLONTI, S. GLASAUER, AND U. BÜTTNER FIG . 4. Response vector orientations for (A) 79 vertical canal-related neurons and (B) 25 otolith-related neurons in FN. Length of vector indicates sensitivity (imprs 01 )/(degrs01 ). A: although neurons with orientations in all directions are present, there is a clear preference, both in terms of numbers and sensitivities, for neurons with iAC and iPC orientations. B: otolith-related neurons are less common than vertical canal-related neurons. In comparison, there is also a lack of highsensitivity neurons and a noticeable absence of pitch neurons. ND, nose down; NU, nose up. ulation of ú0.2 (imprs 01 )/(degrs01 ) (sensitivity criterion) during yaw stimulation ( g Å 07 ). It also has to be considered that an interaction of a VC and an HC input could be additive or subtractive for yaw stimulation in the erect position. A cAC, cPC, and type I response would add and the opposing combination (iAC, iPC, and type I) would subtract (see APPENDIX ). High sensitivity values [e.g., ú1.0 (imprs 01 )/(degrs01 ) (VCP) and ú0.8 (imprs 01 )/(degrs01 ) (roll)] were found for seven of the VCP neurons and one of the five roll neurons tested during yaw stimulation. The remaining 16 (of 24) neurons tested had values below this calculated threshold. From this it can be concluded that the yaw response for these 16 neurons in the erect position is at least partly determined by an HC input. In agreement with this, the modulation of these HC-related neurons should increase during nose-down ( g Å /207 ) earth-vertical axis stimulation. An example of this is shown in Fig. 5. For the seven VCP-related neurons with sensitivities ú1.0 and responses during yaw stimulation at g Å 07 [iAC / type II; iPC / type I (n Å 5); iPC / type II], the relative contribution of the VCs and HCs was calculated (see APPENDI X ). For five neurons [iPC / type II; iPC / type I (n Å 4)] the modulation was indeed mainly determined by the VC input, but for the remaining two neurons the yaw response was due predominantly to the HC stimulation. For the five neurons that only received a VC input, the sensitivity should decrease during g Å /157 earth-vertical axis stimulation, which was indeed seen in one neuron tested. We also tested whether high-sensitivity VCP neurons showed a predicted yaw response. This applied to 3 of 10 / 9k0e$$mr20 J523-6 neurons. Theoretically this could result from subtractive interaction of VC and HC inputs as seen in some of the examples described above. Similarly we determined for the high-sensitivity roll neuron the relative contribution of the roll response to the yaw response. Also for this neuron the yaw response was predominantly determined by the HC input with the VC inputs interacting in a subtractive fashion. Other high-sensitivity roll neurons [ ú0.8 (imprs 01 )/(degrs01 ); n Å 2] were not tested during yaw stimulation. In summary, we conclude that 19 (of 24) neurons responding to yaw stimulation in the erect position had an additional HC input, but that for the remaining 5 neurons the yaw response reflected a VC input. Of these 19 HCrelated neurons, 13 showed convergence between the HC and one VCP pair. Of the remaining neurons, five were roll neurons and one was a pitch neuron. During yaw stimulation, HC-related neurons had on average a phase advance relative to head velocity of /167 and a sensitivity ranging from 0.23 to 1.24 ( imprs 01 ) / ( degrs01 ) ( Table 1 ) . Finally, it was also possible that an HC-mediated response leads to modulation during roll stimulation. This was seen in one roll neuron with a yaw sensitivity ú0.8 (imprs 01 )/ (degrs01 ), actually the same neuron in which the VC (roll) sensitivity also interacted with the yaw response under our stimulus conditions. In this example, the numerical analysis (see APPENDI X ) showed an unexpectedly high contribution of the HC [contributions to sensitivity (imprs 01 )/ (degrs01 ): ipsilateral HC (iHC), 1.7; iPC, 0.8; iAC, 0.5]. 09-02-97 13:54:50 neupa LP-Neurophys FASTIGIAL ACTIVITY IN 3D HEAD MOVEMENTS 1439 FIG . 5. Averaged responses of a canal-related neuron in the right FN that receives convergent input from a vertical canal (A and B; iAC) and a horizontal canal (C and D; type I). Left: stimulus velocity for vertical canal stimulation. Right: stimulus velocity for horizontal stimulation. Two stimulus cycles are repeated for clarity. During vertical stimulation the neuron has its maximal response (A) at b Å 477 and null response (B) close to b Å 0457. During yaw stimulation the response is larger in D ( g Å /207 ) than in C ( g Å 07 ), i.e., when the horizontal canal is close to optimal stimulation. During vertical (A) and horizontal (D) stimulation, neuronal activity leads stimulus velocity. From this it can be concluded that the roll response was determined by an additive 33% HC input to the VC input. In contrast, the yaw response due to the HC input was reduced by 16% by the VC input, which proves that stimulation around the earth-horizontal axis alone is not sufficient to discriminate between VC-VC convergence (roll neurons) or neurons receiving their main input from the HC. All roll neurons investigated received a VC input. Otolith-related neurons On the basis of their phase relation ( {457 around head position), 25 neurons were classified as receiving mainly an otolith input. In many aspects these neurons responded similarly to canal-related neurons. During vertical dynamic stimulation they also exhibited for different head orientations ( Db ) a response maximum and a minimum (null response) 907 apart (Fig. 6). Sensitivity decreased monotonically between maximum and minimum GENERAL CHARACTERISTICS. / 9k0e$$mr20 J523-6 and could be fitted best by a sine function. As for the VCrelated neurons, the phase was constant for different orientations except for a phase shift of 1807 around the null response. The major difference from VC-related neurons and also the reason to classify these neurons as otolith related was that the phase of the neuronal response was close to head position. For the 25 neurons the average phase at 0.6 Hz and the optimal orientation was 0857 (range 0607 to 01337 ), i.e., leading head position by 57. There was no systematic difference of phase relation for neurons with different orientations (Table 2). Although fewer otoliththan canal-related neurons were recorded, most orientations except pitch neurons were encountered (Table 2, Fig. 4B). Otherwise there was no obvious preference for response vector orientations. The response amplitudes were similar for different orientations (Table 2, Fig. 4B). Also the average sensitivity [0.62 (imprs 01 )/(degrs01 )] during dynamic stimulation was RESPONSE VECTOR ORIENTATION. 09-02-97 13:54:50 neupa LP-Neurophys 1440 C. SIEBOLD, L. GLONTI, S. GLASAUER, AND U. BÜTTNER FIG . 6. Otolith-related neuron recorded in the left FN during dynamic vertical (0.6 Hz, A–C) and static roll (D) and pitch (E) stimulation. During dynamic stimulation, neuronal activity (A and B) is in phase with head position (vertical dashed lines). Orientation is close to maximal in A and close to the null response in C. Static response increases during LED and ND. The calculated response vector orientation was b Å 0557 for the dynamic condition and b Å 0487 for the static condition. / 9k0e$$mr20 J523-6 09-02-97 13:54:50 neupa LP-Neurophys FASTIGIAL ACTIVITY IN 3D HEAD MOVEMENTS 1441 FIG . 7. Otolith-related neuron recorded in the left FN during static roll (A) and pitch (B) stimulation. Static response increases from RED to LED and from ND to NU. Despite the irregularity of the neuronal responses, there are clear differences of average responses between different static positions. comparable with that of the canal-related neurons [0.8 (imprs 01 )/(degrs01 )]. However, in comparison there was a clear lack of high-sensitivity neurons (Fig. 4). STATIC TILT. Of 25 neurons, 10 were additionally tested during static tilt. Seven of these neurons were also modulated during static tilt (Figs. 6, D and E, and 7) and three were not. For the modulated neurons the static and dynamic response vector orientation was similar, with differences not exceeding 157. The position-related sensitivity (imprs 01 /deg) was for all neurons higher during dynamic [average 0.6 (imprs 01 )/(degrs01 ), corresponding to 2.33 imprs 01 /deg, range 1.08–3.08 imprs 01 /deg] than during static (average 1.03 imprs 01 /deg, range 0.47–1.92 imprs 01/degrs 01 stimulation. Three neurons with dynamic sensitivities ranging from 1.44 to 3.84 imprs 01 /deg were not modulated at all during static stimulation ( {207 ) in the roll and pitch planes. HC STIMULATION. Of 18 neurons investigated, 11 had in addition to the otolith-related response a modulation during yaw stimulation, which was for 10 neurons a type I response and for 1 a type II response. The remaining seven neurons were not modulated during yaw stimulation. Sensitivity during yaw stimulation ranged between 0.54 and 0.78 (imprs 01 )/(degrs01 ) and the phase advance relative to head velocity averaged /31.57. These values were similar to those values of the VC-related neurons (Table 1). / 9k0e$$mr20 J523-6 The same considerations as for the VC-related neurons with regard to erect head position during yaw stimulation were also made for the otolith-related neurons. The percentage of yaw-responding otolith-related neurons (61%) was actually higher than that of VC-related neurons (35%). As for the VC-related neurons, there was also no preference for any combination of the yaw response (in nearly all instances type I) and the response vector orientation. None of the otolith neurons tested for yaw response had a sensitivity ú1.0 (imprs 01 )/(degrs01 ) (or 0.8 for the roll-related neurons). Thus on the basis of the arguments given above for the VC-related neuron the yaw response for all otolith-related neurons could at least be partially related to an HC input. There was also no high-sensitivity otolith-related neuron among those neurons that did not respond during yaw stimulation. Complex neurons GENERAL CHARACTERISTICS. Seven neurons were classified as complex neurons. Of these, six did not follow the pattern described above for canal- and otolith-related neurons, i.e., their response vectors at different orientations could not be fitted by a sine function with a 1807 phase shift around the null response. For four neurons there was no null response and the phase varied continuously with different orientations, although phase changes were steeper around the minimal response (Baker et al. 1984a). One neuron had a constant 09-02-97 13:54:50 neupa LP-Neurophys 1442 C. SIEBOLD, L. GLONTI, S. GLASAUER, AND U. BÜTTNER sensitivity and phase relationship at all orientations except a null response around b Å 0607 with a 1807 phase shift, and for another neuron a null response was present over a range of Db Å 457. Finally, one neuron with a head velocityrelated sensitivity as seen for the canal-related neurons and a response to static tilt was included in this group, although such response combinations could reflect an otolith input (Schor et al. 1985). STATIC TILT AND HC STIMULATION. Of six complex neurons tested, five responded to static tilt. This reflects an otolithrelated input and is in good agreement with present concepts about ‘‘complex’’ vestibular responses. These require convergence from neurons with different orientations (response vectors) and frequency responses. For the latter at least one otolith-related input is required (Baker et al. 1984b). One type I response was encountered in five complex neurons tested during yaw stimulation. Anatomic location According to the reconstructions there was no systematic distribution of neurons with different response vector orientations. This was true for the rostral-caudal, mediolateral, and ventral-dorsal extent of FN. Vestibular-only neurons responding to vertical dynamic stimulation appeared to be located over the whole FN, being less frequent in the caudal third. On single electrode tracks the most dorsal and most ventral vestibular neuron could be separated by 2.4 mm. This covers most of the ventrodorsal diameter of FN, which is up to 2.5 mm in the monkey. There was some tendency for iAC neurons to be more rostral than iPC neurons, but certainly neurons with either orientation could be recorded on one electrode penetration. The lack of a systematic distribution of response vector orientations is also supported by the analysis of single electrode tracks. It showed that 94% of tracks with more than one vestibular-only neuron contained neurons with more than one orientation. On individual tracks, up to four different orientations, including ipsi- and contralateral orientations, could be encountered (Fig. 8). However, there was also some indication of clustering for certain orientations revealed by the analysis of the remaining 6% of the tracks. On these tracks all vestibular neurons had the same orientation for up to nine neurons on one track. In 24% of the tracks, three to four neighboring neurons had the same or adjacent response vector orientations. The otolith-related neurons were found intermingled with VC-related neurons. Also, the otolith-related neurons did not show a specific spatial distribution of response vector orientations. DISCUSSION Studies of the vestibular nerve provide detailed knowledge as to which information from the canal and otolith organs reaches central nervous structures (Goldberg and Fernandez 1984). It has been shown in several studies that 1) the activity of many vestibular nuclei neurons can be related to individual canal pairs, 2) the responses for a large number of neurons indicate canal-canal or canal-otolith convergence with the same spatial orientation, and 3) only a minority of neu- / 9k0e$$mr20 J523-6 rons shows a complex response pattern reflecting convergence of neurons (with ¢1 otolith input) with different spatial and temporal properties (Baker et al. 1984a,b; Endo et al. 1995; Iwamoto et al. 1996; Kasper et al. 1988). This is also the pattern found in FN during dynamic vertical stimulation. Because we investigated neurons only at one frequency (0.6 Hz), it is conceivable that some of our neurons classified as canal neurons are actually reflecting an input from dynamic otolith afferents. Such neurons have been encountered in the vestibular nuclei after plugging of all six semicircular canals (Schor et al. 1985). Dynamic otolith neurons do not encode head position at most frequencies and can alter their phase relation by up to 1807 at different frequencies (Schor et al. 1985). Thus they could potentially encode head velocity at just 0.6 Hz (the frequency in this study). However, we feel that this is unlikely for the vast majority of neurons. Preliminary (unpublished) results in this laboratory also indicate that the VC-related FN neurons remain in phase with head velocity at different frequencies, with little change in sensitivity (related to head velocity), similarly to what has been described for HC-related neurons in FN (Büttner et al. 1991). Nearly 30% of the neurons responding to vertical dynamic stimulation reflect an otolith input, on the basis of a phase relationship close to head position during dynamic stimulation and responses to static tilt. This has not been reported before in the monkey. In a previous study (Gardner and Fuchs 1975) mainly aimed at horizontal vestibular responses, only a small number of neurons was tested during vertical stimulation, which easily explains how these otolithrelated neurons might have been missed. Our findings are in agreement with an earlier study in the decerebrate cat (Ghelarducci 1973), in which neurons responding to static tilt had been encountered. Noticeable pitch orientations for otolith-related neurons, either up or down, were missing. This lack of pitch orientations has also been reported for vestibular nuclei neurons (Schor et al. 1984). The response vector orientations during dynamic and static stimulation were always similar and supported the assumption that the responses reflected an otolithrelated input. The dynamic sensitivity was always higher than the static sensitivity, as in the vestibular nuclei (Schor et al. 1985) and vestibular nerve afferents (Fernandez and Goldberg 1976). A few otolith-related neurons did not respond during static stimulation but responded only during dynamic stimulation. Considering that in vestibular nerve afferents the sensitivity during static and dynamic stimulation can differ by a factor of 10 (Fernandez and Goldberg 1976), it is conceivable that the small angles of static tilt used in this study and the irregular discharge rate of FN neurons prevented the detection of a possible static response. The static responses of our otolith-related neurons, with a monotonic increase or decrease of activity during different static head positions, reflected basically an utriculus input (Goldberg and Fernandez 1984). However, our limited number of neurons certainly does not exclude the presence of neurons with sacculus-related responses with a decrease or increase of activity in both directions deviating from the erect head position. It also has to be considered that the range of angles investigated ( {207 ) was small, and that the high coefficient of 09-02-97 13:54:50 neupa LP-Neurophys FASTIGIAL ACTIVITY IN 3D HEAD MOVEMENTS 1443 FIG . 8. Semischematic drawing of a transverse section through FN combined with a reconstruction of 2 electrode tracks with vestibularly related neurons. The track on the right yielded vestibular-related neurons (n Å 8) that all had the same response vector orientation (cR, contralateral roll). For the track on the left, among 11 vestibular-related neurons 4 major orientations (dP, cR, iAC, iPC) were encountered. Tracks with multiple orientations were more common than those with only 1 orientation. IN, interpositus nucleus; IV, fourth ventricle. variation of the interspike interval of FN neurons makes it difficult to establish smaller activity changes. A high percentage of otolith-related neurons also responded to yaw stimulation. This reflects an otolith-HC interaction, a feature also commonly found in vestibular nuclei neurons (Bush et al. 1993). Surprisingly, there was only a small number of complex neurons reflecting spatiotemporal convergence. This is surprising for a number of reasons. First, complex responses are assumed to reflect an otolith-VC (or otolith-otolith) interaction in which the various inputs differ in their dynamic response properties and their response vector orientations (Baker et al. 1984a). Considering that many of our otolith-related neurons also reflect an HC input, one also might expect considerable otolith-VC interaction. It is possible that neurons have to be tested over a wider frequency range to obtain more indication of complex responses. Second, responses in FN might be expected to differ more from the primary vestibular input than the vestibular nuclei because of the more numerous stages of processing: this is certainly not supported by the present data. Third, it has been suggested that complex responses are less frequent in the decerebrate state (Baker et al. 1985): this is supported neither by our data nor by recent data from the cat in which the same paradigms were used in the alert and decerebrate preparation (Iwamoto et al. 1996). Comparison with vestibular nuclei neurons For reasons given above, a comparison with vestibular nuclei neurons should be restricted to vestibular-only nonoculomotor neurons. Most of related studies have been performed in the vestibular nuclei of the cat (Baker et al. / 9k0e$$mr20 J523-6 1984a,b; Endo et al. 1995; Iwamoto et al. 1996; Kasper et al. 1988). The results show that a high percentage of neurons receives either a VC-related or an otolith-related input. Complex neurons are rare, and most neurons respond to excitation from one ipsilateral canal. HC-VC convergence is more common than ipsilateral VC-VC convergence (roll neurons). Contralateral inputs are rare. Canal-related pitch neurons, indicating convergence from ipsilateral and contralateral VCs, are generally not encountered in the vestibular nuclei. There is also evidence for convergence from all three canal pairs on individual vestibular nuclei neurons (Baker et al. 1984b). A predominant input from ipsilateral vertical semicircular canals to the vestibular nuclei is also supported by recordings from the alert monkey (Reisine and Raphan 1992). Besides this, there is only sparse information about canal interaction in the vestibular nuclei of the alert monkey (Phillips et al. 1992). According to this preliminary study, type II (horizontal) vestibular nuclei neurons generally also respond during pitch stimulation, whereas type I neurons do not. On the basis of this comparison it can be concluded that, similar to the vestibular nuclei, neurons in FN show a clear preference for ipsilateral canal orientations. It appears that response vector orientations are more widely distributed in FN. Particularly, pitch neurons, which have not been encountered in the vestibular nuclei, are present. Whether this convergence of contra- and ipsilateral canal inputs is actually achieved at the cerebellar level has yet to be determined. Comparison with other cerebellar structures Vestibular responses have been mainly studied in the vestibulocerebellum (flocculus, nodulus, uvula). It should be 09-02-97 13:54:50 neupa LP-Neurophys 1444 C. SIEBOLD, L. GLONTI, S. GLASAUER, AND U. BÜTTNER emphasized that the nodulus receives a major direct vestibular nerve input. A recent study (Barmack et al. 1993) demonstrated that 70% of the vestibular nerve afferents in the rabbit project at least as collaterals to the vestibulocerebellum. The main output from the vestibulocerebellum is to the vestibular nuclei, thus comparable with the projection from the vermis to FN. P cells in the flocculus can carry a precise vestibular signal, with many neurons reflecting convergence from multiple canals (Fukushima et al. 1993; Powell et al. 1996). Otolithrelated responses were not found. This is in contrast to the nodulus-uvula complex, where 40% of the neurons are modulated during static stimulation (otolith input) (rabbit, Barmack and Skojaku 1995). The remaining neurons are activated during VC but not during HC stimulation. The response vector orientations for all these neurons indicate activation of the ipsilateral VCs, mostly of the ipsilateral posterior canal, without evidence for roll or pitch neurons. One major input to FN derives from P cells in the vermis, mainly from the anterior vermis for the vestibular-only neurons under discussion. So far there are no studies investigating P cells in the anterior vermis under natural vestibular stimulation conditions. Earlier studies (Precht et al. 1977) reported polysynaptic vestibular inputs to lobules I–V in the cat. A vestibular input to the anterior vermis is also supported by anatomic studies (Kotchabhakdi and Walberg 1978). spinal mechanisms (Büttner-Ennever 1992). There is also a direct fastigiospinal projection, terminating at the ventral horn in the upper cervical region (Asanuma et al. 1983). Thus efferents from FN can reach spinal motor structures without relaying within the vestibular nuclei. Functional considerations A homunculus-like figure has been attributed to the deep cerebellar nuclei (Thach et al. 1992). With regard to FN, the head would be located in caudal FN and the lower extremities in rostral FN. Vestibular-related neurons in FN could interface with all spinal mechanisms related to posture, gait, and neck movements. From lesion studies it is known that a unilateral FN lesion causes a tendency to fall to the ipsilateral side (Kurzan et al. 1993; Thach et al. 1992). So far nothing is known about how the vestibular neurons in FN affect different muscle groups. It is known that many neck muscles have response vectors toward the pitch axis (Baker et al. 1985; Banovetz et al. 1995), an input not directly provided by vestibular nuclei neurons. It would be of interest to investigate further whether the pitch neurons in FN could provide this input through its fastigiospinal pathway (Asanuma et al. 1983). The present results on FN, with its large variety of response vectors and response combinations, suggest that these muscle requirements could be met very specifically by the fastigial efferents. Afferent connections FN receives an ipsilateral input from the vermis. Lobules I–V project to rostral FN and lobules VI–IX project to caudal FN (Armstrong and Schild 1978; Noda et al. 1990). Also, the nodulus (lobule X) has been reported to project to the ventral region of FN besides its major projection to the vestibular nuclei (Wylie et al. 1994). Occasional collaterals to FN from primary vestibular afferents have been reported (Sato et al. 1989). However, they are sparse enough that a major functional role appears unlikely. Mossy fiber projections from the brain stem are generally bilateral: they derive from all vestibular nuclei (except the lateral vestibular nucleus) (Noda et al. 1990), and include other head movement-related structures (perihypoglossal nuclei, dorsolateral and dorsomedial pontine nuclei, and nucleus reticularis tegmenti pontis) (Gonzalo-Ruiz and Leichnetz 1990; Noda et al. 1990). APPENDIX To decide whether a neuronal response could be attributed to the linear convergence of canal afferents, a least-square fit of the expected response to the found dynamic response patterns was performed. In this way the three weighting factors of each canal direction could be determined. A requirement for this analysis is that the phase of the neuronal response be close to angular velocity over the whole stimulus range, so that the neuron can be classified as being a ‘‘canal only’’ neuron. To simplify the analysis, the semicircular canals were assumed to be perpendicular to each other, with the VCs rotated by a Å 457 with respect to the sagittal plane and the canals tilted backward by w Å 0157. Thus the transformation from head to canal coordinates can be described by the following matrix THC THC Å Efferent connections Most efferent pathways from FN cross within the cerebellum, traverse within the contralateral FN, and leave the cerebellum via the uncinate fasciculus. Crossed fibers terminate in nucleus reticularis tegmenti pontis, dorsomedial and dorsolateral pontine nuclei, and perihypoglossal nuclei (Asanuma et al. 1983; Batton et al. 1977; Noda et al. 1990). The projections from the caudal part of FN (fastigial oculomotor region) are bilateral and mainly to lateral vestibular nucleus and inferior vestibular nucleus. More rostral areas of FN also project to the contralateral medial vestibular nucleus and superior vestibular nucleus (Noda et al. 1990). In general, FN projects mainly to those parts of the vestibular nuclei that are known to be largely involved with vestibulo- / 9k0e$$mr20 J523-6 F cos arcos w sin a 0sin arcos w cos a sin w 0 0cos arsin w sin arsin w cos w G (1) With the rotation angles of the stimulation device defined in METHODS, the transformation matrix from stimulus to head coordinates TSH can be written as TSH Å F cos brcos g sin b 0cos brsin g 0sin brcos g cos b sin brsin g sin g 0 cos g G (2) Thus any stimulus vector s, defined as the direction of an angular velocity vector applied at the position ( b,g ), can be expressed in canal coordinates by the equation r Å THCr TSHr s (3) With the definitions above, the canal coordinate vector r refers to 09-02-97 13:54:50 neupa LP-Neurophys FASTIGIAL ACTIVITY IN 3D HEAD MOVEMENTS positive excitatory responses of the cAC, iAC, and iHC to a neuron in the left hemisphere. For the three paradigms used, Eq. 3 has to be written with the following parameters. 1) Earth-horizontal axis rotation in different yaw orientations (EHY) g Å 0; b varying; sEHY Å [0 1 b Å 90; sEVR Å [0 0 1] T 3) Earth-vertical axis rotation in different pitch orientations (EVP) g varying; b Å 0; sEVP Å [0 0 1] T By defining a gain vector p Å [ ccA ciA ciH ] T with ci being the contributions of the cAC, iAC, and iHC expressed in ( imprs 01 ) / ( degrs01 ) , the answer for a linear canal convergence neuron in response to one of the paradigms above can be expressed as r( b,g ) Å p 7r Å p 7 (THCr TSHr s) (4) where 7 denotes the scalar product. The maximal response of the neuron is then calculated by rmax Å É pÉ. It can be shown that r( b,g ) is a sinusoidal function of the form arsin b / brcos b or arsin g / brcos g for all three paradigms. To evaluate the contribution p of the three canals to the neuronal response r( b,g ) of a single neuron, the theoretical response functions can be fitted to the measured data g( b,g ) of the three paradigms (EHY, EVR, EVP) by a least-square fit ∑ [p 7rEHY ( bi ) 0 gEHY ( bi )] 2 / ∑ [p 7rEVR ( g j ) 0 gEHR ( g j )] 2 i j / ∑ [p 7rEVP ( gk ) 0 gEVP ( gk )] 2 Å min (5) k with i, j, and k being the indexes of single stimulations in the different experimental conditions. Equation 5 can then be solved analyticly for the contribution vector p, which gives the gain factors for the projection of the canal afferents onto the examined neuron. Because positive values for ccA , ciA , and ciH indicate excitatory contributions from the cAC, iAC, and iHC, negative values denote excitatory contributions from the corresponding canals, i.e., iPC, cPC, and contralateral HC. Thus a positive value for ciA denotes contribution from the iAC, and a negative value for ciA denotes contribution from the contralateral posterior canal. As an example, consider a purely VC neuron receiving input from the cAC with a sensitivity of 1.0 (imprs 01 )/(degrs01 ) in the optimal orientation: its contribution vector p (imprs 01 )/ (degrs01 ) is then [1.0 0.0 0.0] T . Inserting p in Eq. 4 predicts a response to earth-vertical (pure yaw) stimulation of r(0.07, 0.07 ) Å 1.0 ∗ cos a∗ sin w Å 00.18 (imprs 01 )/(degrs01 ). Here, the negative value of the sensitivity simply denotes a phase shift of 1807. The signs of the contributions also show whether the neuron receives input from only one side ([ 0, /, / ] or [ /, 0, 0 ]) or from two different sides (all other combinations), with the distribution being a consequence of the coordinate system used. 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