- Email: [email protected]
Is there a vestibular cortex?
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D.F. Clayton and J.M. George – Synucleins in neurobiology and disease
explanations discussed elsewhere23,47,48. Another possibility not yet given much discussion is that the normal appearance of Thr53 in other species might be structurally compensated by a second difference elsewhere in the synuclein sequence: in particular, the human protein is also unique at residue 87 (Ser versus Asn in other species). A precedent for paired compensating mutations has recently emerged from study of the apolipoprotein E gene, where a second mutation nearby in the protein can correct or suppress a mutation that otherwise would disrupt binding to lipoprotein receptors49.
Is there a common denominator?
Acknowledgements The authors’ work was supported by NIH grants NS25742 and AG13762. We thank Brad Hyman and Mike Irizarry for many useful suggestions; Richard Perrin and Benjamin Gantner for help in sequence analyses; and the members of our labs for many valuable discussions.
One has to wonder if the pathology in PD or AD (or both) might be only indirectly related to the normal function of the protein. Perhaps it is simply a major constituent of synaptic specializations, where metabolic turnover may be inefficient and the risk of oxidative damage high. Yet it is also possible that the very properties that accelerate amyloid deposition or precipitate Lewy bodies (or support breast cancer) are central to the normal function of the protein. If a common denominator exists among the disparate pathologies and contexts reviewed here, it would seem to involve the potential for regulated structural interactions with membranes at times or sites of robust physical plasticity, turnover or reorganization. Solving this puzzle will require a mix of tools, approaches and perspectives – but the payoff for both medicine and fundamental neurobiology promises to be high. Selected references 1 2 3 4 5 6 7
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Is there a vestibular cortex? W.O. Guldin and O-J. Grüsser†
W.O. Guldin is at the Freie Universität Berlin, Fachbereich Humanmedizin, Universitätsklinikum Benjamin Franklin, Institut für Physiologie, Arnimallee 22, D-14195 Berlin, Germany. † O-J. Grüsser, deceased in October 1995.
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Very different areas of the primate cortex have been labelled as ‘vestibular’. However, no clear concept has emerged as to where and how the vestibular information is processed in the cerebral cortex. On the basis of data from single-unit recordings and tracer studies, the present article gives statistical evidence of the existence of a well-defined vestibular cortical system. Because the data presented here have been verified in three different primate species, it can be predicted that a similar vestibular cortical system also exists in humans. Trends Neurosci. (1998) 21, 254–259
O
VER THE PAST FEW DECADES, various cortical regions in primates and humans have been labelled as vestibular. By means of evoked potentials, a parietal vestibular field in the rhesus monkey was described, situated at the anterior tip of the intraparietal sulcus and termed 2v (Refs 1,2). Vestibularly driven, single-unit activity was also demonstrated in this field3–6. A cortical
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vestibular representation had been demonstrated years before in the cat by Walzl and Mountcastle by means of evoked potentials7. From case reports of patients with focal lesions in the region of the intraparietal sulcus who experienced vestibular aurae, as well as from studies using electrical stimulation, there is some evidence of vestibular input to the parietal lobe in humans8–10.
Copyright © 1998, Elsevier Science Ltd. All rights reserved. 0166 - 2236/98/$19.00
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W.O. Guldin and O-J. Grüsser – Vestibular cortex
Several reports are also available on vestibular input to different parts of area 7 (Refs 11,12). Vestibular regions in the temporal cortex have been suggested by different authors and studies in humans support this hypothesis10,13–16. In the cat, a vestibular cortical region exists in the cytoarchitectonic area 3a (Ref. 17). The existence of vestibular input to the 3a field in the squirrel monkey (Saimiri sciureus) has been confirmed by recording evoked potentials18 and vestibular input to single neurons19. In the macaque monkey (Macaca fascicularis) there is an extensive vestibular cortical region adjacent to the posterior insula in the depths of the lateral sulcus, termed the parietal insular vestibular cortex (PIVC)20,21; a similar field exists in the squirrel monkey19. In both species, more than 50% of the PIVC neurons are vestibularly driven. The existence of this PIVC area in humans has been demonstrated by testing lesioned patients22 and by positron emission tomography (PET) during vestibular caloric stimulation23,24. Furthermore there is some evidence from electrophysiology1 and anatomy25,26 of vestibular input to the motor area 4. An overview of all regions of the primate cortex that have been labelled as ‘vestibular’ by authors working with primates, including man, is given in Fig. 1 (shaded areas). Note that all these regions were described as vestibular by different investigators, working with different methods in different primate species. From these data several questions arise: (1) Is there more than one vestibular cortical area in any species of primates? (2) If different vestibular cortical regions exist, how are these areas related to each other? (3) Which one is the ‘real’ vestibular cortex? This article endeavours to answer these questions. With this goal in mind, we conducted single-unit recordings in different regions of the cortex in the alert squirrel monkey while looking for vestibularly driven neurons. Our explorations concentrated on regions of the cortex in different species that had been suggested, or proven to be vestibular by other authors. Principally these were the shaded areas shown in Fig. 1. The smaller, black regions in Fig. 1 are the areas in which we could demonstrate vestibularly driven units within a single species of primate: the squirrel monkey.
Vestibular single-unit activity in the primate cortex By means of single-unit recordings, we succeeded in showing the existence of vestibular input to a part of area 3a, area PIVC, area 7, and an area we named VPS (visual posterior sylvian area), as displayed in Fig. 1. By far the greatest number of vestibular units were recorded in the PIVC area; more than 50% of all units had vestibular input. Comparison of their loci with the cytoarchitectonic map allowed us to demonstrate that the PIVC is concordant with the medial part of the retroinsular cytoarchitectonical area (Ri-m)19. This area is situated adjacent to the insula, deep in the lateral sulcus. This is a location very similar to that described in the macaque monkey20,21, but with one difference: the PIVC region in the macaque is placed on the parietal lip of the sulcus, whereas in the squirrel monkey this area is on the temporal lip. Vestibularly driven units in area 7 were found to be very rare; thus, area 7 should not be labelled as a ‘vestibular cortex’. We could also detect vestibularly driven units in the part of the 3a region where the neck muscles are rep-
CS IP 2v 3aNv
Area 7 VPS PIVC Ins.
Fig. 1. The lateral surface of a schematic primate brain; the sylvian sulcus has been unfolded for the purpose of this figure. The shaded regions denote the cumulative extent of all cortical areas labelled as vestibular in primates or in humans. The black regions represent the areas in which vestibular single unit activity has been demonstrated. Abbreviations: CS, central sulcus; IP, intraparietal sulcus; Ins., insular.
resented. Because vestibular-driven units could only be detected in a very small circumscribed area in the neck region of area 3a, surrounded by units with pure somatosensory input, it was not easy to make good estimations about their number. From our small sample we predicted that about 30–50% of the units in the 3a neck region were also driven by vestibular stimuli. We named this locus 3aNv (3a–neck–vestibular region). Our cytoarchitectonic analysis of the recording sites shows that this area is principally within area 3a, but might extend into area 4, the motor cortex. The area 3aNv is probably not concordant with a vestibular region found by evoked potentials in area 3a (Ref. 18), because these authors suggested that the vestibular input to area 3a is to be found in the hand or arm area of 3a. The fourth area where we could record vestibularly driven units in the cortex of the squirrel monkey was area VPS, which is situated posterior to the PIVC; about 30% of the VPS neurons were vestibularly driven or modulated by vestibular stimuli. The difference between the PIVC and the VPS can be accentuated as follows: the PIVC is a vestibular region with optokinetic input whereas the VPS is an optokinetic region with vestibular input. Our data from the macaque monkey provide evidence that a similar area exists in this species as well, but in the parietal bank of the sylvian sulcus. We found optokinetically driven units predominantly in the VPS area, which also has vestibular input but much weaker than in the PIVC. Major efforts to register vestibularly driven units in a region we had suggested as being area 2v in the squirrel monkey were unsuccessful. Nevertheless, we do have anatomical evidence that this area also exists in the squirrel monkey. So in answer to the first question ‘Is there evidence for more than one vestibular area in any species of TINS Vol. 21, No. 6, 1998
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A
B
of tracer made into each single vestibular field in different monkeys. We then summarized the density of retrogradely labelled 23 cortical cells after injections into VC 24 different cortical vestibular areas Area 7 in the squirrel monkey. Thereafter, 2v SII 19 we screened the entire cortical surface of all injected monkeys and PIVC 4 VPS 19 dissected it into pixels. The pixels 5 6 3aNv were squares of either 1 mm in the 6v 3aHv 2 whole brain scheme or 0.5 mm in Ri ld lg T3 8 1 the scheme in the lower part of 3b PA 3a Figs 2 and 3, representing the unfolded lateral sulcus. We calculated the mean density after all 3 injections into the PIVC region. The mean density of expression was allocated a score according to an intensity rating scale: 1, no cells Fig. 2. Precise localization of the vestibular cortical areas revealed in the present paper by statistical analysis of labelled; 2, up to 2 cells labelled; the cortico–cortical connections. Abbreviations: 2v, vestibular region of area 2; 3aHv, 3a–hand–vestibular region; three, 3–5 cells; 4, 6–12 cells; 5, 3aNv, 3a–neck–vestibular region; 6v, vestibular part of area 6; Ig and Id, granular and disgranular insular cortices, 13–25 cells; 6, >25 cells; values represpectively; PA, para-acoustic area; PIVC, parietoinsular vestibular cortex; Ri, retroinsular area; VC, vestibular cingulate resent mean number of labelled cells area; VPS, visual posterior sylvian area. per mm. In the first analysis, all injections were restricted to the PIVC: primates?’: yes, there is compelling evidence from studies the regions that showed outstandingly dense labelling, that is, scored 4, 5 or 6 according to the intensity of the squirrel monkey. rating scale were the cingular sulcus on the mesial corStatistical analysis of vestibular cortex connectivity tex (VC, ‘vestibular’ cingulate region), two regions in To deal with the remaining questions, tracer experi- area 3a, the anterior ventral part of the premotor area ments were carried out. The tracer injections were 6, the area VPS, the posterior insula, parts of area 7 made after the injection sites had been identified elec- and a dense region at the border of areas 2, 5 and 7; trophysiologically by single-unit recordings in awake this coincides exactly with the description given to monkeys. All injected regions, however, had one char- the site where area 2v in the rhesus monkey was localacteristic in common: they were involved in some ized5. Thus there is good evidence of the existence of way or other in vestibular information processing. The this vestibular cortical area in the squirrel monkey. single injection sites and cortico–cortical connections The same procedure was used to analyse the mean have been described elsewhere19. distribution of cortical units that project into area For the present review, we carried out a statistical 3aNv. All three injections were placed into the part of analysis of the total data available from three injections the 3a neck region where vestibularly driven units had been recorded. Labelling appeared in a small region situated in the A B ventro-lateral part of area 3a. A very similar pattern to the projections of the PIVC appeared. Intensity ratings 23 of 4, 5 and 6 were found in the 24 VC anterior ventral part of the pre2v motor area 6 in the VC, in two parts Area 7 SII 19 of area 3a, in area 7, in area 2v, in PIVC the posterior insula and in the PIVC. VPS 4 19 In this study, no labelling was 5 6 3aNv found in the VPS area. 6v 3aHv 2 Ri A similar statistical analysis was ld lg T3 8 1 used for all injections placed into 3b PA the VPS area, under electrophysio3a logical control. Strong labelling (levels 4, 5 and 6) was found in the cingulate cortex and the premotor area 6. After tracer injections into the VPS region, labelling accumulated in a small area inside 3a, Fig. 3. Statistical analysis of the cortical efferents to the vestibular brainstem nuclei in the squirrel monkey. 2v, which differs from the 3aNv area. vestibular region of area 2; 6v, vestibular region of area 6; 3aHv, 3a–hand–vestibular region; 3aNv, 3a–neck–vestibular Exactly the same area was labelled region; Ig and Id, granular and disgranular insular cortices, respectively; PA, para-acoustic area; PIVC, parietal insular after all injections in the areas vestibular cortex; Ri, retroinsular cortex; SII, somatosensory area II; T3, temporal area 3; VC, vestibular cingulate area; 3aNv and PIVC, as described above. VPS, visual posterior sylvian area. We called this area 3aHv for the 256
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3a–hand–vestibular region, and suggested that it is identical to the vestibular area described in area 3a of the squirrel monkey18. Afferents to area VPS are also labelled in area 7, area 2v and in the PIVC, but there is no input to VPS from area 3aNv; however, there is additional input from an area inside the superior temporal sulcus (STS): the medial superior temporal area (MST). From all the pixels (squares) with very dense labelling, that is, they exhibited either level 5 (more than 16 cells mm–2) or level 6 (more than 25 cells mm–2), we then selected only those that displayed such intense labelling after injections in at least two different vestibular cortical areas. Finally, we obtained the picture shown in Fig. 2. Here, seven different labelled areas can be seen: area 2v, the PIVC, area VPS, the anterior ventral part of area 6 (6v, vestibular part of area 6), the areas 3aNv and 3aHv and an area inside the cingulate sulcus in the mesial cortex (VC); labelling in the PIVC was markedly dense. We postulate that these are the areas that are involved in cortical vestibular information processing and comprise a cortical vestibular system.
Cortical projections to the vestibular nuclei We obtained further evidence of the existence of a vestibular cortical system by summarizing the data during other tracer experiments in three different primate species: the squirrel monkey, the macaque monkey and the marmoset (Callithrix jacchus). In all three species, retrograde tracers were injected into the vestibular brainstem nuclei, while verifying the locus of injection with single-unit recordings. The labelled units from each single injection over the entire cortex have been documented elsewhere27–29. For the present paper we generated a cumulative map of all labelled units after all injections to the vestibular nuclei in the squirrel monkey and the macaque. In Fig. 3 only those cortical areas in which the cumulative density of labelling was high (>10 labelled cells mm–2) or very high (>20 labelled cells mm–2) are displayed, and labelling appeared after at least two injections at different points of the vestibular brainstem nuclei. In squirrel monkeys, eight different injections to different parts of the vestibular nuclei were analysed. A pattern of labelled regions becomes visible (Fig. 3) that is very similar to the one already known from the data of cortico–cortical connections in the squirrel monkey presented in Fig. 2. Easily discernible are area 2v, both vestibular regions of the cytoarchitectonical area 3a, the area 3aNv and the area 3aHv, the area 6v region, the cingulate region (VC), the VPS region, the posterior insular cortex and, of course, the PIVC. This perfect concordance between the vestibular cortical system as revealed by cortico–cortical connections and that revealed by cortico–vestibular nuclei connections cannot be purely coincidental. The labelling is clearly restricted to only seven different regions. Analogous experiments in Callithrix and macaque monkeys reveal a pattern of cortico–vestibular projections very similar to that in the squirrel monkey28,29. Figure 4 summarizes the data of cortico–cortical interconnections in the squirrel monkey with respect to the density, thus providing an answer to the second question of how the different areas of the vestibular cortical system are related to each other. Strong interconnections exist between the different cortical regions involved in vestibular information processing, but the PIVC is the only vestibular cortex
3aNv
4
3aHv 2v SII
7b 7a 6v VPS
PIVC lg 8a
MST VC Fig. 4. The cortico–vestibular system and its interconnections. Black arrows indicate very dense projections and grey arrows indicate those of moderate density. Stippled areas are those cortical areas in which vestibular input has been verified in the squirrel monkey by our own single-unit experiments. Areas partly stippled are the ones where we could find anatomical evidence for involvement in the vestibular cortical system. Areas with elliptical borders are those into which tracer injections described in this paper have been placed. When projections are labelled as unidirectional, information about the reciprocity of these interconnections is lacking.
that receives input from all other areas suggested to be part of this vestibular cortical system. The third question, which asked which one is the real vestibular cortex, can be answered: there is no ‘real’ vestibular cortex but a very ‘real vestibular cortical system’ in which the PIVC as the core region plays a central role.
What does the vestibular cortical system look like? The quantitative analysis of the data from our tracer experiments presented in this article has been able to resolve the controversies that still exist over the location of the vestibular cortex. We have demonstrated that a cortical vestibular system exists, and that it consists in the squirrel monkey of at least seven different regions. This vestibular system can be documented in an Old World monkey (such as Macaca fascicularis) and in New World monkeys as well (such as Saimiri sciureus and Callithrix jacchus). Accordingly, we can predict that a similar system exists in humans, a prediction that has already been partly substantiated. All the other cortical regions labelled as vestibular by different authors in monkeys and humans and shown in Fig. 1 are distributed over the cortical surface in such a way that the hypothesis that all vestibular effects measured by these authors are caused by the activities of the vestibular cortical system described in this paper can be accepted. On comparing Fig. 1 with Fig. 2, it is understandable why different regions of the primate cortex have been labelled as vestibular by various authors. Our data also predict that the cingulate area VC and area MST should be involved in vestibular cortical information processing. From PET studies, there is some evidence that the cingulate sulcus is activated during caloric vestibular stimulation24. We recently obtained evidence from single unit recordings in the macaque monkey13,30 for the involvement of the MST region in the information processing during head turning and linear acceleration. From our data, a TINS Vol. 21, No. 6, 1998
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Acknowledgements We wish to thank J. Lerch, H. Nitert, J. Petsch, L. Weiss for their help with the technical equipment, Ms D. Starke for the illustrations and Ms J. Dames for her assistance with the manuscript. Supported by the Deutsche Forschungsgemeinschaft – DFG (Grant Gr 161/39).
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vestibular input to area 6v in humans can also be predicted. The verification of this thesis is a task for future research. In this review, it has become apparent that a cumulative quantitative analysis of the afferents of electrophysiologically defined cortical regions can reveal hidden functional systems with high reliability. When a system is described (in this paper) as ‘vestibular’, that these pathways carry much more information of course than that coming from the vestibular receptor organs must be borne in mind. CNS regions as early as the brainstem vestibular nuclei have a multi-modal integration of sensory and motor information. The thalamic afferents of the different cortical regions described here rise from different nuclei carrying information about somatosensory, motosensory and optokinetic systems31. We stated above that 30–50% of the units in the different cortical regions where injections were placed were vestibularly driven. This implies that cortico–cortical fibres were also labelled from non-vestibular units. Thus, these findings indicate not a vestibular cortical system but a multimodal cortical system for posture control. If we state that the PIVC is a core region, this does not mean that it is the primary vestibular cortical input. In our tracer studies, we have shown that the most important cortical projection in the ‘vestibular cortical system’ runs from area 3aNv to the PIVC (Fig. 4). These projections are so-called feed-forward projections19, so it can be predicted that vestibular information reaches the 3a area with a shorter latency than the PIVC area. We think that the PIVC is an area where information from different cortical centres dealing with posture control is unified into a concept of ‘head-in-space’. All these regions shown in Fig. 4 receive vestibular input that has been relayed to different thalamic nuclei, and can therefore carry vestibular information modulated by different sensory or motor systems. This dissimilar input may also point to the functional role of the various cortical ‘vestibular’ regions. The quantitative analysis of tracer data shown in this review has brought to light a cortical system of ‘vestibular’ areas. It is now up to the researchers working with primates and humans to confirm these findings, and, in particular, to show vestibular input to regions of the human cortex not yet demonstrated to be involved in vestibular information processing. Our data have already been confirmed in part by studies in humans. It has been shown by various methods that PIVC can also be found in humans. Brandt and co-workers pointed out that patients with lesions in the PIVC region have significant impairments in the perception of the subjective vertical22. Investigations using modern imaging techniques complement our findings in primates as well23,24,32–35. The vestibular cortical system presented here includes such different cortical regions as the premotor regions of the frontal cortex (area 6v, area VC) as well as parietal areas (area 2v, area 7), temporal areas (VPS and MST) and a central core region called PIVC, consisting of parts of the granular insula and the retroinsular region close to the acoustic cortex. We suggest that these different areas process information concerning head-in-space movement and the movement of the head in relation to other parts of the body. Furthermore, it feeds back such information monosynaptically down to the vestibular brainstem TINS Vol. 21, No. 6, 1998
nuclei. With this output, the vestibular cortical system might be able to have a direct influence on vestibular reflexes. Further investigations of these cortical systems may lead to a better understanding of such clinical symptoms as vertigo, motion sickness and kinetosis. We believe that not just the conscious perception of the effects of kinetosis, but of any kind of vertigo, is associated with the function of the cortical vestibular system. Vertigo is the syndrome most frequently reported by patients in all fields of medical practice. A clinical syndrome reported less often but of great interest for cognitive brain research is the spatial hemineglect (reviewed in Ref. 36). This research could lead to a better understanding of how spatial recognition is organized. Different studies have shown that vestibular stimulation can diminish or even abolish the symptoms of spatial hemineglect37–39. These data indicate that the vestibular cortical system is strongly involved in spatial perception, as well as in the update of the internal representation of position and movement of the body in the surrounding space and in the consolidation of spatial memory40. Selected references 1 Kornhuber, H.H., Fredrickson, J.M. and Figge, U. (1965) Pflügers Arch. Physiol. 283, 20 2 Fredrickson, U. et al. (1966) Exp. Brain Res. 2, 318–327 3 Schwarz, D.W.F. and Fredrickson, J.M. (1971) Science 172, 280–281 4 Büttner, U. and Büttner, U.W. (1978) Brain Res. 153, 392–397 5 Fredrickson, J.M., Kornhuber, H.H. and Schwarz, D.W.F. (1974) in Handbook of Sensory Physiology (Kornhuber, H.H., ed.), pp. 565–582, Springer 6 Fredrickson, J.M. and Rubin, A.M. (1986) in Cerebral Cortex (Jones, E.G. and Peters, A., eds), pp. 99–111, Plenum Press 7 Walzl, E.M. and Mountcastle, V.B. (1949) Am. J. Physiol. 159, 595 8 Foerster, O. (1936) in Handbuch der Neurologie (Bumke, O. and Foerster, O., eds), pp. 358–448, Springer 9 de Morsier, J. (1938) Encéphale 33, 57–75 10 Penfield, W. (1957) Ann. Otol. 66, 691–698 11 Leinonen, L., Hyvärinen, J. and Sovijärvvi, A.R.A (1980) Exp. Brain Res. 39, 203–215 12 Faugier-Grimaud, S. and Ventre, J. (1989) J. Comp. Neurol. 280, 1–14 13 Thier, P. and Erickson, R.G. (1992) Ann. New York Acad. Sci. 656, 960–963 14 Schneider, R.C., Calhoun, H.D. and Crosby, E.C. (1968) J. Neurol. Sci. 6, 493–516 15 Penfield, W. and Rasmussen, T. (1957) The Cerebral Cortex of Man – A Clinical Study of Localization of Function, Macmillan 16 Tuohimaa, P., Schneider, R.C. and Crosby, E.C. (1987) in The Vestibular System: Neurophysiological and Clinical Research (Graham, M.D. and Kemink, J.L., eds), pp. 411–419, Raven Press 17 Sans, A., Raymond, R. and Marty, R. (1970) Exp. Brain Res. 10, 265–275 18 Ödkvist, L.M. et al. (1974) Exp. Brain Res. 21, 97–105 19 Guldin, W.O., Akbarian, S. and Grüsser, O-J. (1992) J. Comp. Neurol. 326, 375–401 20 Grüsser, O-J., Pause, M. and Schreiter, U. (1990) J. Physiol. 430, 537–557 21 Grüsser, O-J., Pause, M. and Schreiter, U. (1990) J. Physiol. 430, 559–583 22 Brandt, T., Dieterich, M. and Danek, A. (1994) Ann. Neurol. 35, 403–412 23 Friberg, L. et al. (1985) Brain 108, 609–623 24 Bottini, G. et al. (1994) Exp. Brain Res. 99, 164–169 25 Asanuma, C., Thach, W.T. and Jones, E.G. (1983) Brain Res. Rev. 5, 237–265 26 Lang, W., Buettner-Enever, J.A. and Büttner, U. (1979) Brain Res. 177, 3–18 27 Akbarian, S., Grüsser, O-J. and Guldin, W.O. (1993) J. Comp. Neurol. 332, 89–104 28 Guldin, W.O., Mirring, S. and Grüsser, O-J. (1993) NeuroReport 5, 113–116 29 Akbarian, S., Grüsser, O-J. and Guldin, W.O. (1994) J. Comp. Neurol. 339, 421–437
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30 Pekel, M. et al. (1996) Soc. Neurosci. Abstr. 22, 1618 31 Akbarian, S., Grüsser, O-J. and Guldin, W.O. (1992) J. Comp. Neurol. 326, 423–441 32 Dupont, P. et al. (1994) J. Neurophysiol. 72, 1420–1424 33 Berthoz, A. (1996) Brain Res. Cogn. Brain Res. 3, 101–113 34 Vitte, E. et al. (1996) Exp. Brain Res. 112, 523–526 35 Wenzel, R. et al. (1996) Brain 119, 101–110
36 Jeannerod, M. (1987) Neurophysiological and Neuropsychological Aspects of Spatial Neglect, North–Holland 37 Rubens, A.B. (1985) Neurology 35, 1019–1024 38 Karnath, H.O., Christ, K. and Hartje, W. (1993) Brain 116, 383–396 39 Rode, G. et al. (1992) Cortex 28, 203–208 40 Berthoz, A. et al. (1995) Science 269, 95–98
The ‘Ideal Homunculus’: decoding neural population signals Mike W. Oram, Peter Földiák, David I. Perrett and Frank Sengpiel Information processing in the nervous system involves the activity of large populations of neurons. It is possible, however, to interpret the activity of relatively small numbers of cells in terms of meaningful aspects of the environment. ‘Bayesian inference’ provides a systematic and effective method of combining information from multiple cells to accomplish this. It is not a model of a neural mechanism (neither are alternative methods, such as the population vector approach) but a tool for analysing neural signals. It does not require difficult assumptions about the nature of the dimensions underlying cell selectivity, about the distribution and tuning of cell responses or about the way in which information is transmitted and processed. It can be applied to any parameter of neural activity (for example, firing rate or temporal pattern). In this review, we demonstrate the power of Bayesian analysis using examples of visual responses of neurons in primary visual and temporal cortices.We show that interaction between correlation in mean responses to different stimuli (signal) and correlation in response variability within stimuli (noise) can lead to marked improvement of stimulus discrimination using population responses. Trends Neurosci. (1998) 21, 259–265
I
T IS GENERALLY AGREED that perceptions and actions arise from the activity pattern of populations of neurons. In this article, we address the issue of decoding the activity pattern of identified neurons. How the nervous system might decode the population activity is not considered here, but methods by which experimentalists can interpret the relationship between the population activity and either stimulus input or behavioural output are reviewed. Biologically plausible networks have been proposed that implement or approximate the two analysis methods discussed here1,2; indeed, it might not be necessary for the nervous system to carry out explicit decoding. Our aim as experimentalists is to determine what information is present and hence available to the nervous system. Examination of changes in the information content of neural populations allows the underlying processing to be determined. Methods for interpreting the code of an identified population of neurons are therefore a matter of theoretical and practical importance. What could an ideal observer of the activity of a neural population (the ‘Ideal Homunculus’3) infer about the world? It would be useful to employ this method for examining a variety of different neural populations, including peripheral, sub-cortical and cortical populations, because this would allow direct comparison of the results from different brain areas. The method should be independent of the nature of the relationship between the neural response and the stimulus space over Copyright © 1998, Elsevier Science Ltd. All rights reserved. 0166 - 2236/98/$19.00
which it is to operate, especially when we have no clear knowledge or simple geometrical description of the underlying dimensions of neural selectivity. In recent years, experimental data have been collected from a variety of preparations that have been subject to population-level analyses, including preparations recording simultaneously from multiple neurons4–8. The results from these studies have offered insights into neural processing and include data from cat, rat and monkey cortical and sub-cortical areas. The population activities have been interpreted in terms of behavioural output9–21 and sensory input3,21–23. Below we consider two proposed methods for decoding neural population signals: Bayesian analysis3,24 and the population-vector hypothesis11–13,18,19. The effects of correlation of neural variability and signal of the population codes are then examined.
Bayesian and population vector analyses Bayesian inference relies on estimates of the conditional probability distribution of the neuronal responses for each stimulus from a given stimulus set and uses prior probabilities of these stimuli to infer which of these could have caused the observed response, which is expressed as a probability assigned to each stimulus. Subject to the limitations of making such estimates from available data, this method is optimal and theoretically well founded3,24,25. In the case of stimuli with equal prior probabilities, the results are equivalent to that of PII: S0166-2236(97)01216-2
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Mike W. Oram, Peter Földiák and David I. Perrett are at the School of Psychology, University of St Andrews, St Andrews, UK KY16 9JU. Mike W. Oram is currently at the NIMH, Bldg 49 Rm 1B80, NIH, 9000 Rockville Pike, MD 20892, USA and Frank Sengpiel is at the Max-PlanckInstitut für Neurobiologie, 82152 MünchenMartinsried, Germany.
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explanations discussed elsewhere23,47,48. Another possibility not yet given much discussion is that the normal appearance of Thr53 in other species might be structurally compensated by a second difference elsewhere in the synuclein sequence: in particular, the human protein is also unique at residue 87 (Ser versus Asn in other species). A precedent for paired compensating mutations has recently emerged from study of the apolipoprotein E gene, where a second mutation nearby in the protein can correct or suppress a mutation that otherwise would disrupt binding to lipoprotein receptors49.
Is there a common denominator?
Acknowledgements The authors’ work was supported by NIH grants NS25742 and AG13762. We thank Brad Hyman and Mike Irizarry for many useful suggestions; Richard Perrin and Benjamin Gantner for help in sequence analyses; and the members of our labs for many valuable discussions.
One has to wonder if the pathology in PD or AD (or both) might be only indirectly related to the normal function of the protein. Perhaps it is simply a major constituent of synaptic specializations, where metabolic turnover may be inefficient and the risk of oxidative damage high. Yet it is also possible that the very properties that accelerate amyloid deposition or precipitate Lewy bodies (or support breast cancer) are central to the normal function of the protein. If a common denominator exists among the disparate pathologies and contexts reviewed here, it would seem to involve the potential for regulated structural interactions with membranes at times or sites of robust physical plasticity, turnover or reorganization. Solving this puzzle will require a mix of tools, approaches and perspectives – but the payoff for both medicine and fundamental neurobiology promises to be high. Selected references 1 2 3 4 5 6 7
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Is there a vestibular cortex? W.O. Guldin and O-J. Grüsser†
W.O. Guldin is at the Freie Universität Berlin, Fachbereich Humanmedizin, Universitätsklinikum Benjamin Franklin, Institut für Physiologie, Arnimallee 22, D-14195 Berlin, Germany. † O-J. Grüsser, deceased in October 1995.
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Very different areas of the primate cortex have been labelled as ‘vestibular’. However, no clear concept has emerged as to where and how the vestibular information is processed in the cerebral cortex. On the basis of data from single-unit recordings and tracer studies, the present article gives statistical evidence of the existence of a well-defined vestibular cortical system. Because the data presented here have been verified in three different primate species, it can be predicted that a similar vestibular cortical system also exists in humans. Trends Neurosci. (1998) 21, 254–259
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VER THE PAST FEW DECADES, various cortical regions in primates and humans have been labelled as vestibular. By means of evoked potentials, a parietal vestibular field in the rhesus monkey was described, situated at the anterior tip of the intraparietal sulcus and termed 2v (Refs 1,2). Vestibularly driven, single-unit activity was also demonstrated in this field3–6. A cortical
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vestibular representation had been demonstrated years before in the cat by Walzl and Mountcastle by means of evoked potentials7. From case reports of patients with focal lesions in the region of the intraparietal sulcus who experienced vestibular aurae, as well as from studies using electrical stimulation, there is some evidence of vestibular input to the parietal lobe in humans8–10.
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Several reports are also available on vestibular input to different parts of area 7 (Refs 11,12). Vestibular regions in the temporal cortex have been suggested by different authors and studies in humans support this hypothesis10,13–16. In the cat, a vestibular cortical region exists in the cytoarchitectonic area 3a (Ref. 17). The existence of vestibular input to the 3a field in the squirrel monkey (Saimiri sciureus) has been confirmed by recording evoked potentials18 and vestibular input to single neurons19. In the macaque monkey (Macaca fascicularis) there is an extensive vestibular cortical region adjacent to the posterior insula in the depths of the lateral sulcus, termed the parietal insular vestibular cortex (PIVC)20,21; a similar field exists in the squirrel monkey19. In both species, more than 50% of the PIVC neurons are vestibularly driven. The existence of this PIVC area in humans has been demonstrated by testing lesioned patients22 and by positron emission tomography (PET) during vestibular caloric stimulation23,24. Furthermore there is some evidence from electrophysiology1 and anatomy25,26 of vestibular input to the motor area 4. An overview of all regions of the primate cortex that have been labelled as ‘vestibular’ by authors working with primates, including man, is given in Fig. 1 (shaded areas). Note that all these regions were described as vestibular by different investigators, working with different methods in different primate species. From these data several questions arise: (1) Is there more than one vestibular cortical area in any species of primates? (2) If different vestibular cortical regions exist, how are these areas related to each other? (3) Which one is the ‘real’ vestibular cortex? This article endeavours to answer these questions. With this goal in mind, we conducted single-unit recordings in different regions of the cortex in the alert squirrel monkey while looking for vestibularly driven neurons. Our explorations concentrated on regions of the cortex in different species that had been suggested, or proven to be vestibular by other authors. Principally these were the shaded areas shown in Fig. 1. The smaller, black regions in Fig. 1 are the areas in which we could demonstrate vestibularly driven units within a single species of primate: the squirrel monkey.
Vestibular single-unit activity in the primate cortex By means of single-unit recordings, we succeeded in showing the existence of vestibular input to a part of area 3a, area PIVC, area 7, and an area we named VPS (visual posterior sylvian area), as displayed in Fig. 1. By far the greatest number of vestibular units were recorded in the PIVC area; more than 50% of all units had vestibular input. Comparison of their loci with the cytoarchitectonic map allowed us to demonstrate that the PIVC is concordant with the medial part of the retroinsular cytoarchitectonical area (Ri-m)19. This area is situated adjacent to the insula, deep in the lateral sulcus. This is a location very similar to that described in the macaque monkey20,21, but with one difference: the PIVC region in the macaque is placed on the parietal lip of the sulcus, whereas in the squirrel monkey this area is on the temporal lip. Vestibularly driven units in area 7 were found to be very rare; thus, area 7 should not be labelled as a ‘vestibular cortex’. We could also detect vestibularly driven units in the part of the 3a region where the neck muscles are rep-
CS IP 2v 3aNv
Area 7 VPS PIVC Ins.
Fig. 1. The lateral surface of a schematic primate brain; the sylvian sulcus has been unfolded for the purpose of this figure. The shaded regions denote the cumulative extent of all cortical areas labelled as vestibular in primates or in humans. The black regions represent the areas in which vestibular single unit activity has been demonstrated. Abbreviations: CS, central sulcus; IP, intraparietal sulcus; Ins., insular.
resented. Because vestibular-driven units could only be detected in a very small circumscribed area in the neck region of area 3a, surrounded by units with pure somatosensory input, it was not easy to make good estimations about their number. From our small sample we predicted that about 30–50% of the units in the 3a neck region were also driven by vestibular stimuli. We named this locus 3aNv (3a–neck–vestibular region). Our cytoarchitectonic analysis of the recording sites shows that this area is principally within area 3a, but might extend into area 4, the motor cortex. The area 3aNv is probably not concordant with a vestibular region found by evoked potentials in area 3a (Ref. 18), because these authors suggested that the vestibular input to area 3a is to be found in the hand or arm area of 3a. The fourth area where we could record vestibularly driven units in the cortex of the squirrel monkey was area VPS, which is situated posterior to the PIVC; about 30% of the VPS neurons were vestibularly driven or modulated by vestibular stimuli. The difference between the PIVC and the VPS can be accentuated as follows: the PIVC is a vestibular region with optokinetic input whereas the VPS is an optokinetic region with vestibular input. Our data from the macaque monkey provide evidence that a similar area exists in this species as well, but in the parietal bank of the sylvian sulcus. We found optokinetically driven units predominantly in the VPS area, which also has vestibular input but much weaker than in the PIVC. Major efforts to register vestibularly driven units in a region we had suggested as being area 2v in the squirrel monkey were unsuccessful. Nevertheless, we do have anatomical evidence that this area also exists in the squirrel monkey. So in answer to the first question ‘Is there evidence for more than one vestibular area in any species of TINS Vol. 21, No. 6, 1998
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A
B
of tracer made into each single vestibular field in different monkeys. We then summarized the density of retrogradely labelled 23 cortical cells after injections into VC 24 different cortical vestibular areas Area 7 in the squirrel monkey. Thereafter, 2v SII 19 we screened the entire cortical surface of all injected monkeys and PIVC 4 VPS 19 dissected it into pixels. The pixels 5 6 3aNv were squares of either 1 mm in the 6v 3aHv 2 whole brain scheme or 0.5 mm in Ri ld lg T3 8 1 the scheme in the lower part of 3b PA 3a Figs 2 and 3, representing the unfolded lateral sulcus. We calculated the mean density after all 3 injections into the PIVC region. The mean density of expression was allocated a score according to an intensity rating scale: 1, no cells Fig. 2. Precise localization of the vestibular cortical areas revealed in the present paper by statistical analysis of labelled; 2, up to 2 cells labelled; the cortico–cortical connections. Abbreviations: 2v, vestibular region of area 2; 3aHv, 3a–hand–vestibular region; three, 3–5 cells; 4, 6–12 cells; 5, 3aNv, 3a–neck–vestibular region; 6v, vestibular part of area 6; Ig and Id, granular and disgranular insular cortices, 13–25 cells; 6, >25 cells; values represpectively; PA, para-acoustic area; PIVC, parietoinsular vestibular cortex; Ri, retroinsular area; VC, vestibular cingulate resent mean number of labelled cells area; VPS, visual posterior sylvian area. per mm. In the first analysis, all injections were restricted to the PIVC: primates?’: yes, there is compelling evidence from studies the regions that showed outstandingly dense labelling, that is, scored 4, 5 or 6 according to the intensity of the squirrel monkey. rating scale were the cingular sulcus on the mesial corStatistical analysis of vestibular cortex connectivity tex (VC, ‘vestibular’ cingulate region), two regions in To deal with the remaining questions, tracer experi- area 3a, the anterior ventral part of the premotor area ments were carried out. The tracer injections were 6, the area VPS, the posterior insula, parts of area 7 made after the injection sites had been identified elec- and a dense region at the border of areas 2, 5 and 7; trophysiologically by single-unit recordings in awake this coincides exactly with the description given to monkeys. All injected regions, however, had one char- the site where area 2v in the rhesus monkey was localacteristic in common: they were involved in some ized5. Thus there is good evidence of the existence of way or other in vestibular information processing. The this vestibular cortical area in the squirrel monkey. single injection sites and cortico–cortical connections The same procedure was used to analyse the mean have been described elsewhere19. distribution of cortical units that project into area For the present review, we carried out a statistical 3aNv. All three injections were placed into the part of analysis of the total data available from three injections the 3a neck region where vestibularly driven units had been recorded. Labelling appeared in a small region situated in the A B ventro-lateral part of area 3a. A very similar pattern to the projections of the PIVC appeared. Intensity ratings 23 of 4, 5 and 6 were found in the 24 VC anterior ventral part of the pre2v motor area 6 in the VC, in two parts Area 7 SII 19 of area 3a, in area 7, in area 2v, in PIVC the posterior insula and in the PIVC. VPS 4 19 In this study, no labelling was 5 6 3aNv found in the VPS area. 6v 3aHv 2 Ri A similar statistical analysis was ld lg T3 8 1 used for all injections placed into 3b PA the VPS area, under electrophysio3a logical control. Strong labelling (levels 4, 5 and 6) was found in the cingulate cortex and the premotor area 6. After tracer injections into the VPS region, labelling accumulated in a small area inside 3a, Fig. 3. Statistical analysis of the cortical efferents to the vestibular brainstem nuclei in the squirrel monkey. 2v, which differs from the 3aNv area. vestibular region of area 2; 6v, vestibular region of area 6; 3aHv, 3a–hand–vestibular region; 3aNv, 3a–neck–vestibular Exactly the same area was labelled region; Ig and Id, granular and disgranular insular cortices, respectively; PA, para-acoustic area; PIVC, parietal insular after all injections in the areas vestibular cortex; Ri, retroinsular cortex; SII, somatosensory area II; T3, temporal area 3; VC, vestibular cingulate area; 3aNv and PIVC, as described above. VPS, visual posterior sylvian area. We called this area 3aHv for the 256
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3a–hand–vestibular region, and suggested that it is identical to the vestibular area described in area 3a of the squirrel monkey18. Afferents to area VPS are also labelled in area 7, area 2v and in the PIVC, but there is no input to VPS from area 3aNv; however, there is additional input from an area inside the superior temporal sulcus (STS): the medial superior temporal area (MST). From all the pixels (squares) with very dense labelling, that is, they exhibited either level 5 (more than 16 cells mm–2) or level 6 (more than 25 cells mm–2), we then selected only those that displayed such intense labelling after injections in at least two different vestibular cortical areas. Finally, we obtained the picture shown in Fig. 2. Here, seven different labelled areas can be seen: area 2v, the PIVC, area VPS, the anterior ventral part of area 6 (6v, vestibular part of area 6), the areas 3aNv and 3aHv and an area inside the cingulate sulcus in the mesial cortex (VC); labelling in the PIVC was markedly dense. We postulate that these are the areas that are involved in cortical vestibular information processing and comprise a cortical vestibular system.
Cortical projections to the vestibular nuclei We obtained further evidence of the existence of a vestibular cortical system by summarizing the data during other tracer experiments in three different primate species: the squirrel monkey, the macaque monkey and the marmoset (Callithrix jacchus). In all three species, retrograde tracers were injected into the vestibular brainstem nuclei, while verifying the locus of injection with single-unit recordings. The labelled units from each single injection over the entire cortex have been documented elsewhere27–29. For the present paper we generated a cumulative map of all labelled units after all injections to the vestibular nuclei in the squirrel monkey and the macaque. In Fig. 3 only those cortical areas in which the cumulative density of labelling was high (>10 labelled cells mm–2) or very high (>20 labelled cells mm–2) are displayed, and labelling appeared after at least two injections at different points of the vestibular brainstem nuclei. In squirrel monkeys, eight different injections to different parts of the vestibular nuclei were analysed. A pattern of labelled regions becomes visible (Fig. 3) that is very similar to the one already known from the data of cortico–cortical connections in the squirrel monkey presented in Fig. 2. Easily discernible are area 2v, both vestibular regions of the cytoarchitectonical area 3a, the area 3aNv and the area 3aHv, the area 6v region, the cingulate region (VC), the VPS region, the posterior insular cortex and, of course, the PIVC. This perfect concordance between the vestibular cortical system as revealed by cortico–cortical connections and that revealed by cortico–vestibular nuclei connections cannot be purely coincidental. The labelling is clearly restricted to only seven different regions. Analogous experiments in Callithrix and macaque monkeys reveal a pattern of cortico–vestibular projections very similar to that in the squirrel monkey28,29. Figure 4 summarizes the data of cortico–cortical interconnections in the squirrel monkey with respect to the density, thus providing an answer to the second question of how the different areas of the vestibular cortical system are related to each other. Strong interconnections exist between the different cortical regions involved in vestibular information processing, but the PIVC is the only vestibular cortex
3aNv
4
3aHv 2v SII
7b 7a 6v VPS
PIVC lg 8a
MST VC Fig. 4. The cortico–vestibular system and its interconnections. Black arrows indicate very dense projections and grey arrows indicate those of moderate density. Stippled areas are those cortical areas in which vestibular input has been verified in the squirrel monkey by our own single-unit experiments. Areas partly stippled are the ones where we could find anatomical evidence for involvement in the vestibular cortical system. Areas with elliptical borders are those into which tracer injections described in this paper have been placed. When projections are labelled as unidirectional, information about the reciprocity of these interconnections is lacking.
that receives input from all other areas suggested to be part of this vestibular cortical system. The third question, which asked which one is the real vestibular cortex, can be answered: there is no ‘real’ vestibular cortex but a very ‘real vestibular cortical system’ in which the PIVC as the core region plays a central role.
What does the vestibular cortical system look like? The quantitative analysis of the data from our tracer experiments presented in this article has been able to resolve the controversies that still exist over the location of the vestibular cortex. We have demonstrated that a cortical vestibular system exists, and that it consists in the squirrel monkey of at least seven different regions. This vestibular system can be documented in an Old World monkey (such as Macaca fascicularis) and in New World monkeys as well (such as Saimiri sciureus and Callithrix jacchus). Accordingly, we can predict that a similar system exists in humans, a prediction that has already been partly substantiated. All the other cortical regions labelled as vestibular by different authors in monkeys and humans and shown in Fig. 1 are distributed over the cortical surface in such a way that the hypothesis that all vestibular effects measured by these authors are caused by the activities of the vestibular cortical system described in this paper can be accepted. On comparing Fig. 1 with Fig. 2, it is understandable why different regions of the primate cortex have been labelled as vestibular by various authors. Our data also predict that the cingulate area VC and area MST should be involved in vestibular cortical information processing. From PET studies, there is some evidence that the cingulate sulcus is activated during caloric vestibular stimulation24. We recently obtained evidence from single unit recordings in the macaque monkey13,30 for the involvement of the MST region in the information processing during head turning and linear acceleration. From our data, a TINS Vol. 21, No. 6, 1998
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Acknowledgements We wish to thank J. Lerch, H. Nitert, J. Petsch, L. Weiss for their help with the technical equipment, Ms D. Starke for the illustrations and Ms J. Dames for her assistance with the manuscript. Supported by the Deutsche Forschungsgemeinschaft – DFG (Grant Gr 161/39).
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vestibular input to area 6v in humans can also be predicted. The verification of this thesis is a task for future research. In this review, it has become apparent that a cumulative quantitative analysis of the afferents of electrophysiologically defined cortical regions can reveal hidden functional systems with high reliability. When a system is described (in this paper) as ‘vestibular’, that these pathways carry much more information of course than that coming from the vestibular receptor organs must be borne in mind. CNS regions as early as the brainstem vestibular nuclei have a multi-modal integration of sensory and motor information. The thalamic afferents of the different cortical regions described here rise from different nuclei carrying information about somatosensory, motosensory and optokinetic systems31. We stated above that 30–50% of the units in the different cortical regions where injections were placed were vestibularly driven. This implies that cortico–cortical fibres were also labelled from non-vestibular units. Thus, these findings indicate not a vestibular cortical system but a multimodal cortical system for posture control. If we state that the PIVC is a core region, this does not mean that it is the primary vestibular cortical input. In our tracer studies, we have shown that the most important cortical projection in the ‘vestibular cortical system’ runs from area 3aNv to the PIVC (Fig. 4). These projections are so-called feed-forward projections19, so it can be predicted that vestibular information reaches the 3a area with a shorter latency than the PIVC area. We think that the PIVC is an area where information from different cortical centres dealing with posture control is unified into a concept of ‘head-in-space’. All these regions shown in Fig. 4 receive vestibular input that has been relayed to different thalamic nuclei, and can therefore carry vestibular information modulated by different sensory or motor systems. This dissimilar input may also point to the functional role of the various cortical ‘vestibular’ regions. The quantitative analysis of tracer data shown in this review has brought to light a cortical system of ‘vestibular’ areas. It is now up to the researchers working with primates and humans to confirm these findings, and, in particular, to show vestibular input to regions of the human cortex not yet demonstrated to be involved in vestibular information processing. Our data have already been confirmed in part by studies in humans. It has been shown by various methods that PIVC can also be found in humans. Brandt and co-workers pointed out that patients with lesions in the PIVC region have significant impairments in the perception of the subjective vertical22. Investigations using modern imaging techniques complement our findings in primates as well23,24,32–35. The vestibular cortical system presented here includes such different cortical regions as the premotor regions of the frontal cortex (area 6v, area VC) as well as parietal areas (area 2v, area 7), temporal areas (VPS and MST) and a central core region called PIVC, consisting of parts of the granular insula and the retroinsular region close to the acoustic cortex. We suggest that these different areas process information concerning head-in-space movement and the movement of the head in relation to other parts of the body. Furthermore, it feeds back such information monosynaptically down to the vestibular brainstem TINS Vol. 21, No. 6, 1998
nuclei. With this output, the vestibular cortical system might be able to have a direct influence on vestibular reflexes. Further investigations of these cortical systems may lead to a better understanding of such clinical symptoms as vertigo, motion sickness and kinetosis. We believe that not just the conscious perception of the effects of kinetosis, but of any kind of vertigo, is associated with the function of the cortical vestibular system. Vertigo is the syndrome most frequently reported by patients in all fields of medical practice. A clinical syndrome reported less often but of great interest for cognitive brain research is the spatial hemineglect (reviewed in Ref. 36). This research could lead to a better understanding of how spatial recognition is organized. Different studies have shown that vestibular stimulation can diminish or even abolish the symptoms of spatial hemineglect37–39. These data indicate that the vestibular cortical system is strongly involved in spatial perception, as well as in the update of the internal representation of position and movement of the body in the surrounding space and in the consolidation of spatial memory40. Selected references 1 Kornhuber, H.H., Fredrickson, J.M. and Figge, U. (1965) Pflügers Arch. Physiol. 283, 20 2 Fredrickson, U. et al. (1966) Exp. Brain Res. 2, 318–327 3 Schwarz, D.W.F. and Fredrickson, J.M. (1971) Science 172, 280–281 4 Büttner, U. and Büttner, U.W. (1978) Brain Res. 153, 392–397 5 Fredrickson, J.M., Kornhuber, H.H. and Schwarz, D.W.F. (1974) in Handbook of Sensory Physiology (Kornhuber, H.H., ed.), pp. 565–582, Springer 6 Fredrickson, J.M. and Rubin, A.M. (1986) in Cerebral Cortex (Jones, E.G. and Peters, A., eds), pp. 99–111, Plenum Press 7 Walzl, E.M. and Mountcastle, V.B. (1949) Am. J. Physiol. 159, 595 8 Foerster, O. (1936) in Handbuch der Neurologie (Bumke, O. and Foerster, O., eds), pp. 358–448, Springer 9 de Morsier, J. (1938) Encéphale 33, 57–75 10 Penfield, W. (1957) Ann. Otol. 66, 691–698 11 Leinonen, L., Hyvärinen, J. and Sovijärvvi, A.R.A (1980) Exp. Brain Res. 39, 203–215 12 Faugier-Grimaud, S. and Ventre, J. (1989) J. Comp. Neurol. 280, 1–14 13 Thier, P. and Erickson, R.G. (1992) Ann. New York Acad. Sci. 656, 960–963 14 Schneider, R.C., Calhoun, H.D. and Crosby, E.C. (1968) J. Neurol. Sci. 6, 493–516 15 Penfield, W. and Rasmussen, T. (1957) The Cerebral Cortex of Man – A Clinical Study of Localization of Function, Macmillan 16 Tuohimaa, P., Schneider, R.C. and Crosby, E.C. (1987) in The Vestibular System: Neurophysiological and Clinical Research (Graham, M.D. and Kemink, J.L., eds), pp. 411–419, Raven Press 17 Sans, A., Raymond, R. and Marty, R. (1970) Exp. Brain Res. 10, 265–275 18 Ödkvist, L.M. et al. (1974) Exp. Brain Res. 21, 97–105 19 Guldin, W.O., Akbarian, S. and Grüsser, O-J. (1992) J. Comp. Neurol. 326, 375–401 20 Grüsser, O-J., Pause, M. and Schreiter, U. (1990) J. Physiol. 430, 537–557 21 Grüsser, O-J., Pause, M. and Schreiter, U. (1990) J. Physiol. 430, 559–583 22 Brandt, T., Dieterich, M. and Danek, A. (1994) Ann. Neurol. 35, 403–412 23 Friberg, L. et al. (1985) Brain 108, 609–623 24 Bottini, G. et al. (1994) Exp. Brain Res. 99, 164–169 25 Asanuma, C., Thach, W.T. and Jones, E.G. (1983) Brain Res. Rev. 5, 237–265 26 Lang, W., Buettner-Enever, J.A. and Büttner, U. (1979) Brain Res. 177, 3–18 27 Akbarian, S., Grüsser, O-J. and Guldin, W.O. (1993) J. Comp. Neurol. 332, 89–104 28 Guldin, W.O., Mirring, S. and Grüsser, O-J. (1993) NeuroReport 5, 113–116 29 Akbarian, S., Grüsser, O-J. and Guldin, W.O. (1994) J. Comp. Neurol. 339, 421–437
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W.O. Guldin and O-J. Grüsser – Vestibular cortex
30 Pekel, M. et al. (1996) Soc. Neurosci. Abstr. 22, 1618 31 Akbarian, S., Grüsser, O-J. and Guldin, W.O. (1992) J. Comp. Neurol. 326, 423–441 32 Dupont, P. et al. (1994) J. Neurophysiol. 72, 1420–1424 33 Berthoz, A. (1996) Brain Res. Cogn. Brain Res. 3, 101–113 34 Vitte, E. et al. (1996) Exp. Brain Res. 112, 523–526 35 Wenzel, R. et al. (1996) Brain 119, 101–110
36 Jeannerod, M. (1987) Neurophysiological and Neuropsychological Aspects of Spatial Neglect, North–Holland 37 Rubens, A.B. (1985) Neurology 35, 1019–1024 38 Karnath, H.O., Christ, K. and Hartje, W. (1993) Brain 116, 383–396 39 Rode, G. et al. (1992) Cortex 28, 203–208 40 Berthoz, A. et al. (1995) Science 269, 95–98
The ‘Ideal Homunculus’: decoding neural population signals Mike W. Oram, Peter Földiák, David I. Perrett and Frank Sengpiel Information processing in the nervous system involves the activity of large populations of neurons. It is possible, however, to interpret the activity of relatively small numbers of cells in terms of meaningful aspects of the environment. ‘Bayesian inference’ provides a systematic and effective method of combining information from multiple cells to accomplish this. It is not a model of a neural mechanism (neither are alternative methods, such as the population vector approach) but a tool for analysing neural signals. It does not require difficult assumptions about the nature of the dimensions underlying cell selectivity, about the distribution and tuning of cell responses or about the way in which information is transmitted and processed. It can be applied to any parameter of neural activity (for example, firing rate or temporal pattern). In this review, we demonstrate the power of Bayesian analysis using examples of visual responses of neurons in primary visual and temporal cortices.We show that interaction between correlation in mean responses to different stimuli (signal) and correlation in response variability within stimuli (noise) can lead to marked improvement of stimulus discrimination using population responses. Trends Neurosci. (1998) 21, 259–265
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T IS GENERALLY AGREED that perceptions and actions arise from the activity pattern of populations of neurons. In this article, we address the issue of decoding the activity pattern of identified neurons. How the nervous system might decode the population activity is not considered here, but methods by which experimentalists can interpret the relationship between the population activity and either stimulus input or behavioural output are reviewed. Biologically plausible networks have been proposed that implement or approximate the two analysis methods discussed here1,2; indeed, it might not be necessary for the nervous system to carry out explicit decoding. Our aim as experimentalists is to determine what information is present and hence available to the nervous system. Examination of changes in the information content of neural populations allows the underlying processing to be determined. Methods for interpreting the code of an identified population of neurons are therefore a matter of theoretical and practical importance. What could an ideal observer of the activity of a neural population (the ‘Ideal Homunculus’3) infer about the world? It would be useful to employ this method for examining a variety of different neural populations, including peripheral, sub-cortical and cortical populations, because this would allow direct comparison of the results from different brain areas. The method should be independent of the nature of the relationship between the neural response and the stimulus space over Copyright © 1998, Elsevier Science Ltd. All rights reserved. 0166 - 2236/98/$19.00
which it is to operate, especially when we have no clear knowledge or simple geometrical description of the underlying dimensions of neural selectivity. In recent years, experimental data have been collected from a variety of preparations that have been subject to population-level analyses, including preparations recording simultaneously from multiple neurons4–8. The results from these studies have offered insights into neural processing and include data from cat, rat and monkey cortical and sub-cortical areas. The population activities have been interpreted in terms of behavioural output9–21 and sensory input3,21–23. Below we consider two proposed methods for decoding neural population signals: Bayesian analysis3,24 and the population-vector hypothesis11–13,18,19. The effects of correlation of neural variability and signal of the population codes are then examined.
Bayesian and population vector analyses Bayesian inference relies on estimates of the conditional probability distribution of the neuronal responses for each stimulus from a given stimulus set and uses prior probabilities of these stimuli to infer which of these could have caused the observed response, which is expressed as a probability assigned to each stimulus. Subject to the limitations of making such estimates from available data, this method is optimal and theoretically well founded3,24,25. In the case of stimuli with equal prior probabilities, the results are equivalent to that of PII: S0166-2236(97)01216-2
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Mike W. Oram, Peter Földiák and David I. Perrett are at the School of Psychology, University of St Andrews, St Andrews, UK KY16 9JU. Mike W. Oram is currently at the NIMH, Bldg 49 Rm 1B80, NIH, 9000 Rockville Pike, MD 20892, USA and Frank Sengpiel is at the Max-PlanckInstitut für Neurobiologie, 82152 MünchenMartinsried, Germany.
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