2003 – Prague


Eleventh Annual Meeting of ISBN

Date: June 29 – July 3, 2003

Place: Prague, Czech Republic

Venue: Michna Palace

PROGRAM

* indicates potential new member

Sunday June 29, 2003

Arrival, Registration, Welcome Party

Monday June 30, 2003

9:00-9:15 Announcements

Symposium 1 : Sensory Deprivation, Compensation and Neuroplasticity
(Organiser: Alexander Stevens)
9:15– 9:30: Introduction to symposium

Invited Speakers:
9:30 – 10:15 Daphne Bavelier, University of Rochester. Effects of deafness and sign language on visual cognition

10:15 – 11:00 David Corina, University of Washington. Neural plasticity of language function in Deaf signers: Delimiting the scope of change.

Coffee: 11:00-11:30

11:30 – 12:15 Annette Sterr, University of Liverpool. Tactile information processing and attention mechanisms in the blind

12:15 – 1:00 Alexander Stevens, Oregon Health & Science University.
Functional correlates of auditory perception in the blind

1:00-4:00 Lunch and Free time

4:00-6:15 Traditional Paper Session
(Chair: Kate Watkins)

4:00-4:20 Janine Mendola: Abnormal Maps of Retinotopic Space in Adults and Children with Amblyopia

4:20-4:45 Jody Culham*: Object grasping relies on different neural substrates than object recognition: Data from normal subjects and a patient with visual form agnosia.

4:45-5:10 Michael Hunter*: Developing psychophysical models of auditory hallucinations in the functional neuroimaging environment: Stimulus laterality and temporal response dynamics.

5:10-5:40 Break

5:40-6:00 Philip Servos: Talking and Walking Biological Motion: Are they dissociable?

6:00-6:25 Paul Gribble*: Neural Control of Arm Movements: Internal Models of Limb Dynamic


Tuesday July 1, 2003

9:15 – 10:00 Works in Progress Session
(Chairs: Sandy Neargarder and Alice Cronin-Golomb)

9:15-9:30 Kate Watkins: Hemispheric asymmetries in auditory processing of temporal and spectral information: Preliminary results with fMRI

9:30-9:45 Ingrid Johnsrude: The organization of auditory cortex for vowel perception: fMRI studies.

9:45-10:00 Susan Pigott: The Role of the Temporal Lobes in Memory: An Intriguing Case Study.

10-10:15 Break

10:15 –11:15
Presidential Speaker:
Prof. Dr. Angela D. Friederici
Director, Department Neuropsychology
Max Planck Institute of Cognitive NeuroScience
Topic: Traces of auditory language processing in the brain

11.15-11.45 Break

11:45-12:45 Business meeting

Afternoon outing


Wednesday July 2, 2003

Symposium 2 : Individual Differences in Aging

Co-organisers:
Alice Cronin-Golomb, Boston University, USA
Patricia Cowell, University of Sheffield, UK

9:15– 9:30: Introduction to symposium

Invited Speakers:
9:30 – 10:05 Roberto Cabeza*, Duke University. Individual differences in healthy aging: Functional neuroimaging evidence

10:05 – 10:40 Vanessa Sluming*, University of Liverpool. Making Music for a Living: The Brains of Symphony Orchestra Musicians,

Coffee: 10:40-11:10

11:10 – 11:45 Alison Lee*, Bath Spa University. Parkinson’s Disease, visuospatial processing and perception to action.

11:45- 12:20 Rosemary Varley, University of Sheffield. Speech motor learning across the lifespan: from ‘giggles’ to ‘gigabytes’.

12:20-1:00 Panel discussion with speakers and audience

1:00-4:00 Lunch and Free time

4:00-6:00 Traditional Paper Session
(Chair: Susan Pigott)

4:00-4:20 John Desmond : Cerebro-cerebellar circuitry in verbal working memory: Neuroimaging evidence from healthy and alcoholic populations.

4:20-4:40 Julien Doyon: Knitting Functional Patterns: Neural correlates of early learning vs. expert performance of a motor skill.

4:40-5:00 Stefan Kohler: Medial temporal-lobe responses to novel stimuli and novel stimulus relationships: Evidence from event-related fMRI in humans

5:00-5:20 Break

5:20-5:40 Antonio Incisa della Rocchetta: Preserved knowledge of maps of countries: implications for the organisation of semantic memory

5:40-6:05 Ludice Malkova*: Basolateral amygdala and social behavior in monkeys: The effects of reversible drug manipulations of GABAA and glutamate receptor


Thursday July 3, 2003

Traditional Paper Session:- 9:00-10:00
(Chair: Julien Doyon)

9:00-9:20 Robert Stackman: Small conductance calcium-activated K+ channels constrain hippocampal-dependent memory.

9:20-9:40 April Benasich: Children with holoprosencephaly: Origin and propagation of auditory event-related potentials

9:40-10:00 Rebecca Billingsley: Magnetic source imaging of verbal fluency and comprehension in English and Chinese speakers

Coffee and End of Conference


ABSTRACTS

Monday June 30, 2003

Symposium 1 : Sensory Deprivation, Compensation and Neuroplasticity
Organiser: Alexander Stevens, Oregon Health & Science University, USA

Studies in animals and humans have demonstrated that sensory deprivation in one modality can lead to alterations in the perceptual abilities in the remaining senses. Neural systems also show structural and functional changes following deprivation. However, what determines how neural reorganization unfolds, and the relationship between this reorganization and perceptual compensation is unclear. Developmental factors, such as the maturational stage of the nervous system at the time of sensory loss, cause of sensory loss and cross-modal experience are no doubt important in influencing both the perceptual adaptations and underlying neural changes that occur. Furthermore, these factors may have different effects depending on the modality which is lost. The goal of the symposium will be to examine the relationship between perceptual changes that occur following sensory deprivation and the alterations that occur in the neural systems with which they are associated.


Invited Speakers:

1. Effects of deafness and sign language on visual cognition.
Daphne Bavelier, University of Rochester

Do deaf individuals have better vision? A review of the existing evidence suggests that deaf individuals do not have better vision overall. Rather, only some aspects of visual attention appear modified in the deaf. In particular, deaf individuals exhibit enhanced peripheral visual attention. This change seems mediated by the parietal cortex, a known center of visual attention. This change is quite specific to deafness as it is not observed in hearing signers or in hearing individuals who rely heavily on their peripheralvision, such as action video game players. This is not to say that these two kinds of experience, signing and video game playing, do not affect visual cognition. Videogame playing enhances several different aspects of visual selective attention, such as the number of objects that can be apprehended at once and one’s ability at processing fast occurring information in the visual scene. Similarly, signing leads to changes of its own. Motion processing becomes more left lateralized in native signers. The use of signs also leads to mark changes in short-term memory capacity. Overall, our work highlights the specificity of plastic changes, calling for careful investigations of the role of the type of experience, brain systems modified and age of exposure in plastic changes.


2. Neural plasticity of language function in Deaf signers: Delimiting the scope of change.
David P. Corina, University of Washington, Seattle

Recent neuroimaging studies of users of signed languages provide compelling evidence of functional specialization within the left-hemisphere for language processing in the deaf. The observation of left hemisphere function in the mediation of signed languages of the deaf is consistent with data from lesion studies of deaf aphasics. At the same time, these studies have begun to document noted deviations from traditionally expected patterns of language representation, including left and right hemisphere posterior parietal and left temporal fusiform activations. The evidence of functional-anatomical differences between spoken and signed language processing raises important questions with respect to the degree and kind of reorganization that might be possible in the human nervous system. In this talk I will document these facts and discuss these data in relation to models of neural plasticity.


3. Tactile information processing and attention mechanisms in the blind
Annette Sterr, University of Liverpool

A central issue in the investigation of adult human brain plasticity is to characterize the effects of use and training on neural circuitry and it’s linkage with altered behavioral performance and skill acquisition. By the nature of their disability, blind individuals are forced to depend on non-affected modalities for information about their external environment. As indicated by neuroimaging and behavioral experiments, such increased demand on the remaining senses is reflected in a substantial enlargement of primary sensory representations and perceptual phenomena such as tactile mislocalizations. Furthermore, recent ERP data on sustained and selective tactile attention in the blind indicates that visual deprivation may also affect the mechanisms underlying tactile spatial attention.


4. Functional correlates of auditory perception in the blind
Alexander Stevens, Oregon Health & Science University

As a consequence of blindness, auditory perception plays a prominent role in recognition and discrimination of objects and events in the environment. The greater perceptual demands placed on the auditory modality is associated with enhancements on a number of measures of auditory perception. Similarly, auditory based alterations in the functional organization of posterior cortical areas, as measured with fMRI, have been documented, particularly in occipito-temporal areas, where speech-related stimuli seem to produce most salient responses. These perceptual and cortical changes appear to vary as a function of the age at the time of blindness onset. Functional changes in auditory cortical regions appear to be more subtle, and anatomic analysis has not revealed changes in auditory cortex as a result of blindness.


4:00-6:15 Traditional Paper Session

Abnormal Maps of Retinotopic Space in Adults and Children with Amblyopia

Ian P. Conner, Terry L. Schwartz, James V. Odom, & Janine D. Mendola, West Virginia University, Morgantown, WV.

The visual performance of humans with amblyopia (‘lazy eye’) has been described using psychophysical measures, but neurological characterization of the disease is incomplete. The only fMRI study of amblyopia that defined visual area boundaries was limited to maps obtained through the nonamblyopic eye only. This study seeks to determine whether the retinotopic organization in visual cortex mapped through amblyopic eyes are abnormal, as would be predicted by the behavioral measures. We also aim to provide a description of how abnormal early sensory experience rearranges plastic neural circuits in the human brain.
Subjects. Twenty-three adult (age 18-35) and sixteen pediatric (age 7-12) subjects were studied. The participants were divided according to diagnosis (anisometropic amblyopia, strabismic amblyopia, or control). The breakdown according to these diagnoses for the adults was 7/8/8 and 7/4/5 for the children, respectively. All of the strabismic subjects had an inward eye deviation (esotropia). Our subject groups were matched for age and education within cohorts.
Methods The cortical representation of retinotopic visual space was mapped with a phase-encoded design using high contrast, chromatic stimuli. The cardinal axes of space (eccentricity and polar angle) were mapped separately. Each eye was stimulated while the other eye viewed an isoluminant gray screen, and fixation stability was monitored with the Avotec-SMI system. MR images were acquired on a 1.5T GE Signa scanner. Twenty oblique slices of the occipital pole were selected for gradient echo spiral imaging (TR = 4000 ms, TE = 40 ms, FA = 65 deg, FOV = 22 cm, matrix 64 x 64, slice thickness = 4 mm). All functional data sets were first motion corrected and intensity normalized using the FS-FAST analysis tools. Fourier-based analysis was used to correlate the phase of response for each voxel with the retinotopic stimulus location. The resulting data set was displayed on the cortical surface model for each subject created with FreeSurfer.

Result

For both adults and children, the amblyopic eyes showed a reduced representation of the central visual field, consistent with the well known central visual acuity loss of such subjects. Anisometropic adults and children also show disorganized polar angle maps for both eyes. Strabismic adults and children (with inward eye deviation) show polar angle maps with a bias favoring the ipsilateral hemisphere for affect eyes and even fellow eyes, i.e., temporal better than nasal retina. This naso-temporal asymmetry is consistent with psychophysical performance, and can be readily interpreted as evidence for ‘constant’ suppression of the nasal retina by the fellow eye fovea, as the geometry would predict. Furthermore, a subset of strabismic amblyopes exhibits a contralateral hemisphere representation of the amblyopic eye’s temporal retina which is suggestive of abnormal transcallosal connections.

Conclusion

The major subtypes of amblyopia can be distinguished in both adults and children by large scale changes in visual field representation. It is also of considerable broad scientific interest to observe this dynamic “real time” re-mapping of (population) receptive fields that occurs between alternate eye stimulation in subjects with amblyopia.


Object grasping relies on different neural substrates than object recognition: Data from normal subjects and a patient with visual form agnosia.

Culham1, J. C., Danckert1, S. L., James2, T. W., Humphrey1, G. K., Milner,3 A. D. & Goodale1, M. A.
1 Department of Psychology, University of Western Ontario, Canada
2 Vision Research Center, Vanderbilt University, U.S.A.
3 Wolfson Research Centre, University of Durham, U.K.

Although both object recognition and object grasping require processing about shape, size and orientation of the object, different neural substrates appear to be involved. Whereas object recognition is thought to involve the ventral visual stream in occipitotemporal cortex, object grasping is thought to involve the dorsal visual stream in occipitoparietal cortex. We used event-related functional magnetic resonance imaging (fMRI) to identify a specific region of the dorsal stream within the anterior intraparietal sulcus (AIP) that appears to subserve visually-guided grasping. In neurologically-intact subjects, we observed greater activation for grasping compared to reaching in AIP, but not in the lateral occipital (LO) cortex, a ventral stream area that has been implicated in object recognition. In a well-studied patient with visual form agnosia, D.F., structural MRI revealed lesions that were largely confined to the ventral stream LO region, likely accounting for her deficits in visual object recognition. Despite impaired object recognition, D.F.’s has retained the ability to accurately preshape her hand during grasping. Functional MRI revealed activation of parietal cortex during reaching and grasping and greater activity in AIP for grasping compared to reaching. Taken together, these results reinforce the suggestion that visually-guided grasping relies on distinct neural substrates within parietal cortex and does not depend on intact object perception abilities within the ventral stream.

Developing psychophysical models of auditory hallucinations in the functional neuroimaging environment: Stimulus laterality and temporal response dynamics.
Michael D Hunter1, Timothy D Griffiths2, 3, Iain D Wilkinson4, Sean A Spence1 & Peter WR Woodruff1.
1Sheffield Cognition and Neuroimaging Laboratory (SCANLab), Academic Clinical Psychiatry, University of Sheffield, The Longley Centre, Norwood Grange Drive, Sheffield S5 7JT, UK. 2Auditory Group, University of Newcastle, UK. 3Wellcome Department of Imaging Neuroscience, UK. 4Academic Unit of Radiology, University of Sheffield, UK.

Introduction

Our overall aim is to map the normal human brain’s response to phenomenological aspects of hallucination-like speech in order to make predictions regarding the pathogenesis of actual auditory hallucinations in patients. Previously, we have used functional magnetic resonance imaging (fMRI) to demonstrate that auditory association cortex in the left planum temporale (PT) may be critically involved in the perception of the spatial location of human speech sounds (Brain 2003; 126: 161-9). Furthermore, our behavioural data suggest that listeners are more accurate at correctly identifying the spatial location of speech when stimuli are located on the right- than on the left-hand side (Percept Mot Skills, in press). In the current study, we used fMRI to investigate the effect of stimulus laterality on temporal characteristics of the haemodynamic response to hallucination-like speech, in the PT.

Method

Five healthy, right-handed, males were studied. Over electrostatic headphones, 18 hallucination-like speech stimuli (commands uttered by a single male speaker; 3-4 words; 1-2s duration) were lateralised to one side or the other by adjustment of the inter-aural amplitude ratio (9:1 in the required direction). fMRI was performed on a 1.5T Eclipse system at Sheffield University (10 x 6mm slices with 1mm gap, covering all of the temporal cortex; echo time=40ms; repetition time=1s; 450 time points). In an event-related design, stimuli were presented at pseudo-random intervals of 14, 16 or 18s. Subjects underwent 3 functional scans; there were equal numbers of right- and left-lateralised stimuli in each scan (occurring in pseudo-random order) and the content of every individual stimulus was the same in each scan, but laterality of each stimulus was counterbalanced between scans. Images were analysed using statistical parametric mapping in SPM99 (www.fil.ion.ucl.ac.uk/spm).

Result

In a fixed-effects model, group analysis of blood oxygenation level dependent (BOLD) response to all speech was thresholded at p<0.05, corrected for height in the whole brain, and demonstrated activation in left and right superior temporal gyri. We then analysed the time courses of regions of interest derived from spheres of radius 10mm centred on the probabilistic maxima of the left and right PT (Westbury et al., Cereb Cortex 1999; 9: 392-405).
In the left PT, ipsilateral (left-lateralised) speech was associated with mean time to peak BOLD response of 6.41s after stimulus onset, but contralateral (right-lateralised) speech was associated with significantly longer mean time to peak BOLD response of 7.26s (Wilcoxon signed-ranks test; Z=1.89; p=0.03). Contralateral speech was also associated with mean peak BOLD response of 10.34% greater amplitude than ipsilateral speech (Z=1.69; p=0.04).
In the right PT, there was no difference between ipsilateral (right-lateralised) and contralateral (left-lateralised) speech in mean time to peak BOLD response (6.66s & 6.61s, respectively). Contralateral speech was associated with mean peak BOLD response of 32.00% greater amplitude than ipsilateral speech (Z=3.09; p=0.001).

Discussion

Our findings could result from more sustained neural activity in the left PT in response to contralateral than ipsilateral speech, an effect which may not occur in the right PT. This might reflect functional specialisation for language processing in the left PT, manifest as a ‘right ear advantage’ effect in behavioural tasks. Our paradigm may be a useful probe of lateralised brain organisation in patients with actual hallucinations.


Talking and Walking Biological Motion: Are they dissociable?

Philip Servos
Department of Psychology, Wilfrid Laurier University, Waterloo, ON N2L 3C5 Canada

Neuropsychological research suggests that the neural system underlying visible speech on the basis of kinematics is distinct from the system underlying visible speech of static images of the face and identifying whole body actions from kinematics alone. Functional magnetic resonance imaging (fMRI) was used to identify the neural systems underlying point-light visible speech, as well as perception of a walking/jumping point-light body, to determine if they are independent. Although both point-light stimuli produced overlapping activation in the right middle occipital gyrus encompassing area KO and the right inferior temporal gyrus, they also activated distinct areas. Perception of walking biological motion activated a medial occipital area along the lingual gyrus close to the cuneus border, and ventromedial frontal cortex, neither of which was activated by visible speech biological motion. In contrast, perception of visible speech biological motion activated right V5 and a network of motor related areas (Broca=s area, PM, M1, and SMA), none of which were activated by walking biological motion. Many of the areas activated by seeing visible speech biological motion are similar to those activated while speechreading from an actual face, with the exception of M1 and medial SMA. The motor-related areas found to be active during point-light visible speech are consistent with recent work characterizing the human “mirror” system.


Neural Control of Arm Movements: Internal Models of Limb Dynamics
Paul L. Gribble
Dept. Psychology, Dept. Physiology, University of Western Ontario

We are able to move our limbs with remarkable ease, despite the significant mechanical and dynamical complexities that multi-joint motion imposes on the motor system. For example, during movements such as reaching, nonlinear rotational forces arise at one joint due to the motions of adjacent limb segments. Similarly, complex forces may arise due to interactions with the environment (e.g. picking up and moving objects). The degree to which the motor system is able to modify descending control signals to account for the perturbing effects of these factors reflects the extent to which the these loads and their consequences are represented neurally. The idea that the motor system uses “internal models” to plan and control movement has become an important theoretical construct. My research program is focused on understanding the neural and computational mechanisms that underlie internal models for movement planning and motor learning. In this talk I will provide an overview of my recent work with humans and non-human primates that has examined internal representations of multi-joint limb dynamics during reaching and pointing movements.


Tuesday July 1, 2003

9:15 – 10:00 Works in Progress Session

(Chairs: Sandy Neargarder and Alice Cronin-Golomb)

Hemispheric asymmetries in auditory processing of temporal and spectral information: Preliminary results with fMRI

Kate Watkins & Tomáš Paus, Montreal Neurological Institute, McGill University, Montreal, Canada

Zatorre & Belin (2001) used PET to measure the response of the auditory cortex to temporal and spectral variations in the auditory signal. We wish to adapt this paradigm for use in the fMRI environment. This will allow us to measure changes in the brain’s response to such stimuli during childhood and adolescence. In our first pilot subject, we used a long TR (12secs) and regression analyses of the BOLD signal against five levels of increasing spectral or temporal variation. Our preliminary findings indicate that it is feasible to replicate the original PET results using fMRI, even in a single subject. Our work in progress is aimed at reducing the scanning time to around 10 minutes by reducing the TR and the number of stimuli, while hopefully maintaining sufficient statistical power.


The organization of auditory cortex for vowel perception: fMRI studies.

I. Johnsrude, S. Uppenkamp, R. Patterson, A. Hervais-Adelman, D. Norris, M. Davis, W. Marslen-Wilson.

Perception of speech sounds requires many stages of processing in order to extract speech-relevant information from the stream of sound, map this onto stored representations, and combine these representations in order to derive the overall meaning. Early stages must rely on general analytic capacities of the ascending auditory system, and are probably common to all primates. Later, speech-specific, operations are possibly unique to humans, but the earliest of these (relevant to phonemic perception) probably rely on an auditory cortical organization shared with other primates. We conducted two fMRI studies in order to delimit the cortical loci of the earliest stages of processing specific to speech, with reference to the known hierarchical organization of primate auditory cortex (e.g., Kaas & Hackett, 2000). In both studies, normal volunteers were scanned (using sparse imaging) while listening to a variety of vowel, vowel-like, and nonspeech sounds (whole-brain acquisition, 21 slices/3 s; 10 sec TR; 3T Bruker system). T1 weighted structural images were also obtained on each subject, and left and right Heschl’s gyrus (HG) located in each of these by four judges. In Study I, 9 listeners heard natural spoken vowels, synthetic vowels, and three classes of stimuli closely matched to synthetic vowels on long-term energy distribution, one of which was perceived as vowel-like and two of which were not. All sounds, when compared to a silent baseline, strongly activated auditory cortex on HG. When vowel (and vowel-like) sounds were contrasted with those perceived as nonspeech, activation was observed bilaterally in an area below and posterior to HG, in the dorsal bank of the superior temporal sulcus (STS). In Study II, 12 different volunteers listened to 6 classes of stimuli that varied in their similarity to speech sounds, as rated by a separate set of pilot subjects. The stimuli rated as most and least “vowel-like” had also been used in Study I. Activation correlated with vowel-likeness ratings appeared in the same STS area observed in Study I. This area probably corresponds either to parabelt cortex (Kaas & Hackett, 2000) or to polysensory cortex (Seltzer & Pandya, 1994) in the macaque and is therefore at least one, and perhaps up to four, stages of processing removed from primary auditory cortex. This result suggests that speech-specific processing does not begin in primary auditory cortex, and that speech is processed using general auditory mechanisms even at early cortical levels of the ascending auditory system. This work was supported by the Medical Research Council, UK. References: Kaas J, Hackett T (2000) Proc Natl Acad Sci U S A 97:11793-11799; Seltzer B, Pandya DN (1994) J Comp Neurol 343:445-463.


The Role of the Temporal Lobes in Memory: An Intriguing Case Study.

Pigott, S.E. 1, 3, McAndrews, M.P. 2, Stevens, T.K 3, Blume, W. T. 1, 3, Diosy, D. 1, 3 and Bartha, R 4. 1London Health Sciences Centre; 2 University of Toronto, 3 University of Western Ontario; 4 Robarts Research Insititute

A 41 year-old man (P.A.) with temporal lobe epilepsy was evaluated at a surgical epilepsy unit in London, Ontario, Canada. P.A. reported that although he can remember information in the shorter term (e.g. one to two days), he has significant difficulty remembering information over the longer term (e.g. six weeks). He reported essentially no memories for significant life events over the past twenty years such as his wedding and the birth of his children. Standard clinical neuropsychological testing revealed above average intelligence and at least average scores on verbal, visuospatial and problem solving tests. Scores on verbal and visuospatial memory tests with 30 minute delays ranged from low average to above average levels, confirming his impression of relatively good memory for recently presented information. On the Autobiographical Memory Interview, he was able to recall events from the first twenty years of his life with precision but had significant difficulty recalling information from the last twenty years. In contrast, he performed well on a test assessing memory for famous people from the 1970’s through to the 1990’s.

EEG investigations suggested a left temporal lobe seizure focus with interictal abnormalities in both temporal lobes. An MRI revealed as slightly smaller left temporal pole and a questionable signal abnormality in the left hippocampus. Short echo time 1H MR spectroscopy data were acquired on a Siemens/Varian 4T MRI scanner in the left and right posterior hippocampi. Levels of N-acetylaspartate (NAA)- a putative measure of neuronal function-were decreased by more that 60% in the left (3.3 mM) and the right hippocampi (2.6 mM) compared to average healthy control levels (9.2 +/- 2.0mM). Results will be discussed with respect to current theories of memory function and the role of temporal lobe structures in memory consolidation and in the retrieval of different types of memories.


Wednesday 2 July, 2003

Symposium 2 : Individual Differences in Aging

Co-organisers:
Alice Cronin-Golomb, Boston University, USA
Patricia Cowell, University of Sheffield, UK

Individual Differences in Aging

This symposium will examine the effects of age on neurocognitive systems during adulthood. Both healthy and pathological processes will be explored in a manner that sheds light on behavioural resilience vs. decline in later life. Topics covered by invited speakers include “neurocognitive asymmetry in high and low performing older adults”, “age and musicians’ brains”, “motor speech systems across the life span” and “visuospatial cognition in Parkinson’s Disease”. Discussion on the environmental, medical and developmental factors that contribute to individual differences in aging provides a common theme across these specialist areas. Introductory overview, concluding remarks, and discussion will be led by the organisers.


1. Individual differences in healthy aging: Functional neuroimaging evidence

Roberto Cabeza, Center for Cognitive Neuroscience, Duke University

Whereas some older adults show significant cognitive deficits, others perform as well as young adults. To investigate the neural basis of these different aging patterns, we measured brain activity in low- and high-performing older adults using positron emission tomography (PET). In functional neuroimaging studies, prefrontal cortex (PFC) activity tends to be less asymmetric in older than in younger adults (Hemispheric Asymmetry Reduction in Old Adults or HAROLD). This finding has been observed in the domains of episodic retrieval, episodic encoding/semantic retrieval, working memory, perception, and inhibitory control. Age-related asymmetry reductions may help counteract age-related neurocognitive decline (compensation hypothesis) or they may reflect an age-related difficulty in recruiting specialized neural mechanisms (dedifferentiation hypothesis) To compare these two hypotheses, we measured PFC activity in young adults, low-performing older adults, and high-performing older adults during recall and source recognition of recently studied words. Low- and high-performing older participants were selected before scanning from a larger sample of older adults. Compared to recall, source memory was associated with right PFC activations in young adults. Low-performing older adults recruited similar right PFC regions as young adults, whereas high-performing older adults engaged PFC regions bilaterally. Thus, consistent with the compensation hypothesis and inconsistent with the dedifferentiation hypothesis, a hemispheric asymmetry reduction was found in high-performing but not in low-performing older adults. These results suggest that low-performing older adults recruited a similar network as young adults but used it inefficiently, whereas high-performing older adults counteracted age-related neural decline through a plastic reorganization of neurocognitive networks.


2. Making Music for a Living: The Brains of Symphony Orchestra Musician

Vanessa Sluming1,2 and Neil Roberts2, 1Department of Medical Imaging and 2Magnetic Resonance and Image Analysis Research Centre, University of Liverpool, Liverpool, L69 3GB, UK

Current imaging techniques have substantially increased the range of tools available for in vivo brain exploration and complement neurophysiological and neuropsychological methods of investigation. Performing musicians form an intriguing subject pool to study the association between skill acquisition and brain structure and function. The unique training, motor and auditory experiences of musicians provide an ideal experimental design to investigate whether cerebral adaptations in response to skill learning or sensory stimulation correlate with micro- and macro-structural cortical changes. Studies using a variety of imaging techniques have provided evidence to support the notion of use-dependent neuroplastic adaptation associated not only with acquiring but also with maintaining, to a high level, musical performance skills. Symphony orchestra musicians use these acquired skills as their occupation, and maintain a high standard of performance ability throughout their adult working life. Consequently, they offer the ideal opportunity to investigate how maintenance of specific acquired occupational skills interact with age-related alterations in brain structure and cognition, thus contributing to individual differences in healthy aging.


3. Parkinson’s Disease, visuospatial processing and perception to action.

Alison Lee, Department of Psychology, Bath Spa University, UK

There is increasing evidence that the progression and symptoms of Parkinson’s disease (PD) vary according to the side of the brain where the initial motor systems begin. For example, those who have a left-sided onset (and therefore presumably right-sided brain damage) show a small but consistent rightwards bias when asked to bisect a line. This bias is amplified when the to-be-bisected line is presented on the right of a page or screen. Those whose disease began with right-sided motor symptoms will show a smaller (but still consistent) bias to the left. A further illustration that the perception of space is impaired in PD comes from the comments of those who freeze in doorways. Some respond that they momentarily “feel too large” to pass through a doorway. When tested in a laboratory study, PD patients with left-sided onset preferred to fit though a virtual doorway that was 160% wider on average than their shoulder width. Those with right-sided onset selected a doorway that was only 3% wider than their body width. A healthy age-matched control selected an average width of 16% wider than their bodies. These results suggest that for those with left-sided PD onset, space seems compressed whereas those with right-sided PD onset show a slight expansion. These observations could help understand the various motor problems suffered by PD sufferers as well as providing useful information about the brain bases of visuospatial processes.


4. Speech motor learning across the lifespan: from ‘giggles’ to ‘gigabytes’

Rosemary Varley, Department of Human Communication Sciences, University of Sheffield, UK

The number of words known and used by healthy adults is conservatively estimated at around 50,000. The majority of these words are acquired early in the lifespan, and there is evidence from second language learning that the capacity to establish new native-like phonetic plans diminishes with age. There is growing evidence that the age at which a word is acquired is an important variable in determining processing in healthy speakers and understanding patterns of deficit in acquired neurogenic disorders such as apraxia and aphasia. But within the overall picture of age-related decline in speech motor learning, there are indications of individual variation. Some acquired speech disorders, for example, foreign accent syndrome, generally are found in younger female speakers. From these observations of age- and sex-linked differences in word production mechanisms it is possible to develop new models of speech motor learning and to re-examine the neurocognitive basis of speech control, with potential insights into the nature and management of a variety of disorders of speech.


4:00-6:00 Traditional Paper Session

(Chair: Susan Pigott)

Cerebro-cerebellar circuitry in verbal working memory: Neuroimaging evidence from healthy and alcoholic populations.

John E. Desmond1,2, S. H. Annabel Chen1, Matthew P. Kirschen1, Eve DeRosa3, Adolf Pfefferbaum3,4, and Edith V. Sullivan2,3.

Departments of 1Radiology, 2Neurosciences Program, 3Psychiatry and Behavioral Sciences, Stanford University, Stanford CA, USA, and 4Neuroscience Program, SRI International, 333 Ravenswood Ave, Menlo Park, CA.

Previous neuroimaging investigations of healthy adult subjects have demonstrated that both superior (HVI) and inferior (HVIIB) regions of cerebellar cortex show increased activation during high load relative to low load conditions during a Sternberg verbal working memory task. Our recent work indicates that these cerebellar activations are predominately linearly related to working memory load. Event-related fMRI investigations, using individual estimates of hemodynamic response function derived from the cerebellum, indicate that the cerebellar response begins at the initial, or encoding, phase of the Sternberg task in which 2-6 letters are briefly visually presented to the subject for short-term storage. Both left prefrontal and right superior cerebellar regions, two regions that are neuroanatomically connected via cortico-pontine and ponto-cerebellar pathways, activate in tandem during this phase of the task, suggesting that this cerebro-cerebellar network is involved in the rapid encoding of the consonant sequence needed to initiate the phonological loop. The importance of this network to normal verbal working memory performance is demonstrated by comparing the high versus low load activation difference in alcoholic relative to matched non-alcoholic control subjects. This comparison revealed that, despite identical behavioral performance in alcoholics and controls, left prefrontal cortex (BA 44) and right superior cerebellum (HVI) activations were significantly different between the groups, with greater activation observed in alcoholics than in controls. These results suggest that the cerebro-cerebellar network that supports the articulatory control system of verbal working memory may require a compensatory increase in alcoholics in order to maintain the same level of performance as controls. Supported by NIMH (MH60234) and NIAAA (AA10723, AA05965).


Knitting functional patterns : neural correlates of early learning vs. expert performance of a motor skill.

J. Doyon1,4,5*, R. Amsel2, R. Bouras1, O.Monchi1,4, V. B. Penhune3,5, & M. Petrides2,5.

Departments of psychology, 1 University of Montreal, 2 McGill University, 3 Concordia University, 4 Institut Universitaire de Gériatrie de Montréal, Université de Montréal, 5 McConnell Brain Imaging Center, McGill University, Montreal, Canada.

Previous imaging studies of motor skill learning, defined as the process by which movements come to be performed effortlessly with practice, have focused on identifying the cerebral structures critical in the early acquisition phase of a motor behavior. Thus little is known with respect to the anatomical system mediating the performance of over-learned, fully-automatized skills. This experiment used fMRI to examine the brain regions active while highly skilled knitters performed either their usual (fully-automatized) North American technique or a new (early acquisition) Continental technique learned prior to scanning. The subjects (n=8, >20 years of experience) were scanned in three conditions: a) executing a series of simple stitches using their usual technique (“Old”); b) executing the same stitches using the new technique (“New”); c) performing alternating simple movements with the two needles (control). The number of movements made were equated across conditions. Whole brain, BOLD was acquired using single-shot, echo-plannar imaging on a 1,5T Siemens magnet (TR=3s, TE=40ms, 642 matrix, FOV=24cm), and the data were analysed using the FMRIstat family of software developed at the Montreal Neurological Institute (Worsley et al., 2002). Contrast between the “New” and “Control” conditions revealed increased activity in motor-related structures like the premotor cortex, the putamen/globus pallidus and cerebellum (Lobules V and VI) bilaterally, as well as in the right thalamus, anterior cingulum and SMA. By contrast, comparison of the “Old” and “Control” conditions yielded an increase of activity only in the right inferior parietal cortex and in the SMA and putamen/globus pallidus regions bilaterally, the latter basal ganglia structure remaining significantly active when fMRI signals in the “New” condition were subtracted from the “OLD”. These findings are consistent with the model recently proposed by Doyon and Ungerleider (2002), which suggests that early learning of a sequential motor task necessitates the contribution of both cortico-cerebellar and cortico-striatal systems, but that after the skill has become fully automatized, the cerebellum is no longer essential, and the long lasting representation of the skill now involves the basal ganglia and associated motor cortical regions.


Medial temporal-lobe responses to novel stimuli and novel stimulus relationships: Evidence from event-related fMRI in humans

Stefan Köhler, Lindsay S. Howland, Stacey Danckert, & Joe Gati

University of Western Ontario and The John P. Robarts Research Institute, London, Ontario, Canada

Functional neuroimaging research has shown that processing of novel complex visual scenes produces robust activation in the human medial temporal lobe (MTL), including the hippocampus. It has been suggested that this activation reflects the detection of novel stimulus relationships. In the first of two event-related fMRI experiments, we tested this hypothesis by examining whether the same MTL regions that respond to scene novelty also respond when subjects aim to detect novel relationships of the kind typically embedded in scenes, namely object-place and object-object relationships. During scanning, subjects were asked to detect, among a majority of previously studied familiar object pairs, pairs that were altered (i.e. novel) in terms of either object-place or object-object relationships. In addition, subjects were scanned while processing novel as compared to familiar scenes. We found that right hippocampal and parahippocampal regions that showed a scene-novelty response responded to both novel object-place and novel object-object relationships; by contrast, a left hippocampal region only responded to novel object-object relationships. These findings indicate that hippocampal and parahippocampal regions involved in scene processing support the detection of novel stimulus relationships; they also show a lateralization pattern that maps well onto findings from lesion studies. In a follow-up experiment currently underway in our lab, we address to what extent the MTL response to novel stimulus relationships depends on whether their processing is required by the task at hand, and whether the novelty response is limited to complex stimuli with embedded relationships.

Preserved knowledge of maps of countries: implications for the organisation of semantic memory
Antonio Incisa della Rocchetta and Lisa Cipolotti, Department of Neuropsychology (Box 37), The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom

Objective

Our aim was to clarify the cognitive processes and the neural structures underlying the selective preservation of the category of countries.

Method

We investigated one patient (DB) who suffered from a series of cerebral infarcts and one patient (WH) who suffered from semantic dementia; we administered them a wide variety of cognitive tests, including semantic and perceptual tasks.

Result

We found that patient DB had a severe perceptual impairment, including dense apperceptive agnosia, prosopagnosia and topographical agnosia. Despite these deficits, he could effortlessly name countries from their outline maps. Patient WH had severe and widespread naming and comprehension difficulties, encompassing a large number of semantic categories. Remarkably, the category of countries was selectively preserved.

Conclusion

We documented the selective preservation of the category of countries. This provides an opportunity to evaluate current theories of the cerebral organisation of semantic memory. The perceptual model of category-specific effects (Humphreys and colleagues) does not provide an adequate account of the country preservation in the context of severe perceptual impairment. The evolutionary account (Caramazza and colleagues) needs to envisage the possibility that some categories of knowledge, such as countries, may not be pre-wired, but learned during ontogenetic development. The ontogenetic model (Warrington and collaborators) needs to envisage a spatial channel for the development of maps knowledge. We conclude that maps are represented in a spatial/topological channel, which involves the right parietal region and parahippocampal structures.


Basolateral amygdala and social behavior in monkeys: The effects of reversible drug manipulations of GABAA and glutamate receptor

L. Malkova, L.L.Lower, K. Gale

Bilateral ablations of the medial temporal lobes, or the amygdala (Am) alone, induced profound changes in socioemotional behavior, including decrease in social interactions and increase in self-directed activities. Our goal is to determine whether similar behavioral effects can be achieved acutely by reversible drug manipulations of GABA and glutamate receptors within various subdivisions of Am. Here we investigated the effects of either activation or inhibition of Am by uni- or bilateral infusions of various drugs into basolateral nuclei (BLA) on social interactions in 7 juvenile pigtailed macaques. Baseline behavior in dyads was assessed prior to drug infusions. After each infusion each monkey was paired with a nontreated control, their behavior was videotaped, and compared (ANOVA) with the respective baseline (including saline) for each of the observed dyads. At least three sessions for each drug in each monkey alternated with baseline sessions. We examined these manipulations: 1. Activation of Am by GABAA antagonist bicuculline methiodide (BMI), 2. Inhibition of Am by GABAA agonist muscimol (MUS), 3. Inhibition of Am by blockade of glutamate receptors, either NMDA by AP-7 or AMPA by NBQX. Infusion of BMI resulted in decrease of social interactions (p<0.05), with a complete loss of contact play, and in emergence of self-directed activities and active withdrawal. Infusion of MUS resulted in increase in social contact (p<0.05), especially in affiliative social interactions such as grooming (p<0.05), while rough-and-tumble play and locomotion decreased. By contrast, blockade of each glutamate receptor type resulted in overall decrease of general activity level (decrease in manipulation and locomotion and increased passivity; all ps<0.05) but no significant changes in social interactions were observed. The effects of reversible drug manipulations are consistent with some of the effects of Am lesions. The studied neurotransmitters may contribute differently to various components of social behavior.
Supported by CAN, HD3997, NS20576.


Thursday July 3, 2003

Traditional Paper Session:- 9:00-10:00

(Chair: Julien Doyon)

Small conductance calcium-activated K+ channels constrain hippocampal-dependent memory.

Robert W. Stackman*1, Rebecca S. Hammond1, Thanos Tzounopoulos1,2 and John P. Adelman2, 1Dept of Behavioral

Neuroscience and 2Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.

Alterations in the excitability of hippocampal neurons influence spatial and nonspatial hippocampal-dependent memory. Small-conductance Ca2+-activated K+ (SK) channels underlie the medium component of the afterhyperpolarization (mAHP) that follows an action potential. Blocking SK channels with the bee venom toxin, apamin abolishes the mAHP and enhances neuronal excitability. SK channel subtypes are differentially distributed within the hippocampus, with SK2 present in considerably higher densities than SK1 or SK3. This presentation will discuss data from a series of studies examining the influence of SK channels on hippocampal memory and physiology in mice. Our initial studies have found that apamin enhanced the induction of hippocampal synaptic plasticity and enhanced spatial and non-spatial hippocampal-dependent memory encoding in mice after systemic injection. These data suggest that blocking SK channels removes a constraint on hippocampal memory mechanisms. We are currently examining hippocampal memory and physiology in transgenic mice that overexpress SK2 or SK3 channels. The goal of these studies is to identify the SK channel subtype that underlies the effects of apamin. Pyramidal cell recordings in hippocampal slices prepared from SK2 mice (10-fold overexpression relative to wild type) revealed a significantly larger amplitude mAHP than that of wild type mice. Mice that overexpress SK2 channels exhibited a significant impairment of spatial learning and memory in the hidden platform Morris water maze task. The spatial memory impairment of SK2 mice was not due to noncognitive performance deficits since there was no difference in swim speed, thigmotaxis, or escape latency to a visible platform compared to wild type mice. A 3-fold overexpression of SK3 channels affected neither the hippocampal mAHP, nor spatial learning and memory in the Morris water maze task. Together these data suggest that SK2, but not SK3, channels inhibit hippocampal memory and it’s underlying physiological mechanisms.


Children with holoprosencephaly: origin and propagation of auditory event-related potentials

A.A. Benasich, H. Jing; J. Flax; C.P. Roesler, Center for for Molecular & Behavioral Neuroscience, Newark, NJ, USA

Holoprosencephaly (HPE) is a birth defect that results in incomplete cleavage of the embryonic forebrain into cerebral hemispheres. Children with HPE, who survive the first year of life, can expect to have relatively long life spans. Affected children may have multiple cognitive and physical anomalies, including facial dysmorphisms such as cleft lip and/or palate, severe motor delays, and little or no expressive language. We have been using converging methodologies, including EEG/ERPs and auditory and visual perceptual-behavioral paradigms, adapted from our infant assessment batteries, to characterize brain and behavior relations in HPE. One perceptual substrate shown to be critically involved in normal development of language is rapid temporal processing (RTP) of auditory information. RTP was assessed in a group of affected children using auditory brain event-related potentials (ERPs). The purpose of this study was to localize the origin and propagation of ERP components in children with semi-lobar HPE. Patterns of brain activation (e.g. mismatch negativity [MMN]) to rapid auditory sequences and direction, time course, and amplitude of brain activation were examined. Results were compared with those of age-matched and cognitively-matched control groups. ERPs were recorded to 100-100 Hz standard and to 100-300 Hz deviant stimuli (15%) in a MMN paradigm. Latency and amplitude of the MMN-like component were measured. Source of ERP components was estimated using BESA. Directed coherence was calculated to demonstrate signal transmission among brain regions. MMN was seen in all HPE children but with longer latency. Directed coherence analyses suggested that signals propagated between left and right frontal areas use the same frequency band in both HPE and control children but differed as to intensity. Decreased coherence, but higher directed coherence was observed in lower frequency bands in the HPE children. These data suggest less efficient development of neuronal networks and differing organization of cortical substructures for sensory processing in HPE.
Supported by: The Don & Linda Carter Foundation and NICHD RO1-HD29419.


Magnetic Source Imaging of Verbal Fluency and Comprehension in English and Chinese Speaker

Rebecca L. Billingsley1*, Panagiotis G. Simos1, Wenbo Zhang1, Fernando Maestú2, Christina Valaki,3 Shirin Sarkari1, Eduardo M. Castillo1, Ekaterina Pataraia1, Andrew C. Papanicolaou1

1 Division of Clinical Neurosciences, Department of Neurosurgery, University of Texas – Houston Medical School, Houston, Texas, USA
2 Centro de Magnetoencefalografia Dr Perez Modrego, Universidad Complutense, Madrid, Spain
3 Department of Methodology, History and Theory of Science, Cognitive Science Division, University of Athens, Greece

There is a wealth of lesion evidence, cortical stimulation data, and non-invasive functional brain imaging data regarding the cortical mechanisms that support expressive and receptive language functions in native speakers of Indo-European languages. Less is known about the lateralization and timing of neurophysiological activity involved in linguistic processing in the context of other language groups, with distinct features in both their written or spoken forms, like the Chinese. The prosodic features of Mandarin Chinese are used to distinguish words that are, otherwise, phonologically identical. The presence of fundamentally distinct features in Mandarin Chinese raises the question of whether the cerebral mechanisms involved in language functions in native Chinese speakers are different from those used by speakers of non-tonal languages. One such difference may involve increased participation of the right hemisphere. Two magnetic source imaging studies will be described in which the spatio-temporal profiles of the mechanisms of word production and comprehension were compared in English and Chinese speakers. Using the high spatio-temporal resolution of this imaging modality, the validity and reliability of which have been previously demonstrated with intracarotid amobarbital and electrocortical stimulation mapping studies, we found differences between these language groups in the relative degree of hemispheric asymmetry of neurophysiological activity in anterior and posterior cortical language areas. Group differences were also found in the onset of activity in these areas during the comprehension and production of single words. The results from these studies support the presence of distinct neurophysiological mechanisms for the English compared with the Mandarin Chinese language.