Dr. Igor Kagan
Head of Decision and Awareness Group, German Primate Center (DPZ)
Kellnerweg 4, Goettingen 37077, Germany
http://www.dpz.eu/dag
Decision making: monkeys & humans
Our research aims to understand the neural basis of cognitive functions such as spatial
awareness and decision making: the ability to perceive and to act adequately in response to
multiple external sensory events, exhibiting a flexible behavior in face of several alternatives.
We are utilizing neurophysiological recordings (neuronal firing and local field potential) in
behaving macaque monkeys, functional imaging (fMRI) in monkeys and humans, and
reversible perturbations (inactivation and stimulation) of specific brain regions to study
these functions on the local (neuronal) and global (network) levels. Our current work is
focusing on intra-areal, interhemispheric, and pulvinar-cortical interactions and
communication during visuomotor decision making and response selection, a monkey model
of spatial neglect and decision making deficits, and monkey-human comparison of these
functions.
Human-monkey comparison of visuomotor processing
Most of the current knowledge about the mechanisms underlying visuospatial and
visuomotor processing is derived from electrophysiological recordings in macaques, and
more recently from functional imaging experiments in humans. Due to an important need to
integrate results from both types of studies, it is tempting to simply equate
electrophysiology and imaging data. However, the relationship between human imaging and
Dr. Igor Kagan
Head of Decision and Awareness Group, German Primate Center (DPZ)
Kellnerweg 4, Goettingen 37077, Germany
http://www.dpz.eu/dag
monkey electrophysiological studies is often not clear because of differences between the
two species and the complicated relationship between electrophysiological and fMRI signals.
To facilitate the integration of human and monkey data, and to investigate inter-species
similarities and differences from the evolutionary perspective, we study both species by
means of the same method, fMRI. In order to link fMRI activations to underlying neuronal
activity we perform analogous experiments using electrophysiological recordings in
monkeys. In particular, we are interested in comparing cerebral asymmetry and
lateralization patterns for spatial and effector representations.
On the methodological level, we apply the time-resolved event-related approach to both
monkey and human imaging. This allows investigating dynamic brain activity originating from
specific task epochs, for example cognitive decision and planning signals that bridge sensory
input and motor output events in the delay response paradigms.
Intra- and interhemispheric interactions during decision-making
Dr. Igor Kagan
Head of Decision and Awareness Group, German Primate Center (DPZ)
Kellnerweg 4, Goettingen 37077, Germany
http://www.dpz.eu/dag
The ability to explore and flexibly decide between multiple response options is an important
and highly developed attribute of primate behavior. A central question towards
understanding the neural mechanisms of goal-directed behavior is how the distributed
activity in multiple brain areas is integrated within and across the two hemispheres. For
example, the circuitry underlying spatial decisions encompasses a bihemispheric network, in
which each hemisphere represents predominantly contralateral response options. Thus,
when a primate is faced with multiple response options in opposite visual hemifields, how
does brain activity in the two hemispheres converge to a specific decision? Existing models
postulate inter-hemispheric competition and/or cooperation, but how the signals from the
two hemispheres interact is not known, and direct neuronal evidence for interhemispheric
competition is scarce. We are addressing these questions using event-related fMRI and bihemispheric neuronal recording during free- and reward-based choice tasks.
Cortical and thalamic mechanisms of spatial awareness and neglect
The intact visual awareness of space around us is an emergent property of activity in the two
brain hemispheres. Following a damage to certain regions in one hemisphere, the
perception and action in the contralesional hemispace are impaired, leading to spatial
neglect syndrome. The dominant model of spatial neglect, the interhemispheric opposition,
or rivalry theory, postulates mutually suppressive interactions between two hemispheres
that are in equilibrium in the normal state, and whose balance is disturbed following the
lesion. This theory is corroborated by stimulation studies showing that inhibition of the
healthy hemisphere may alleviate neglect symptoms. However a direct neuronal evidence
Dr. Igor Kagan
Head of Decision and Awareness Group, German Primate Center (DPZ)
Kellnerweg 4, Goettingen 37077, Germany
http://www.dpz.eu/dag
for the proposed interhemispheric suppression is still largely missing. The study of basic
neglect mechanisms in human patients is hindered by large and variable lesions, lack of prelesion "baseline" data, and medical considerations.
Using local reversible pharmacological inactivation of MRI-targeted brain areas, we are
studying the basic mechanisms of spatial disorders and recovery in a monkey model. Since
pharmacological agent action is limited to several hours, inactivation experiments in
combination with fMRI or electrophysiological recordings can be performed repeatedly in
the same subject, both in normal and lesioned states. Using this technique, we are hoping to
gain insight into the dynamic interactions between areas within each hemisphere and
between hemispheres that underlie spatial neglect and recovery.
Role of thalamo-cortical interactions in cortical communication and visuomotor
coordination
The thalamic pulvinar has greatly enlarged during primate evolution in parallel with cortical
areas subserving visuomotor functions. Key visuomotor cortical regions to which the
pulvinar reciprocally connects are the posterior parietal and the frontal cortices. Although
Dr. Igor Kagan
Head of Decision and Awareness Group, German Primate Center (DPZ)
Kellnerweg 4, Goettingen 37077, Germany
http://www.dpz.eu/dag
communication between frontal and parietal areas can be mediated by direct corticocortical connections, recent theories have highlighted a possible contribution of the pulvinar
to cortical communication. This notion is supported by our recent studies showing abnormal
BOLD signal in parieto-frontal areas and sensorimotor and movement decision deficits as a
consequence of reversible pulvinar inactivation. By means of combined reversible
inactivation and electrophysiological and fMRI recordings we are investigating the
contribution of the pulvinar to communication in frontoparietal circuits.
“Functional imaging reveals rapid reorganization of cortical activity after parietal
inactivation in monkeys” (Melanie Wilke, Igor Kagana and Richard A. Andersen; 2012)
Impairments of spatial awareness and decision making occur frequently as a consequence of
parietal lesions. Here we used event-related functional MRI (fMRI) in monkeys to investigate
rapid reorganization of spatial networks during reversible pharmacological inactivation of
the lateral intraparietal area (LIP), which plays a role in the selection of eye movement
targets. We measured fMRI activity in control and inactivation sessions while monkeys
performed memory saccades to either instructed or autonomously chosen spatial locations.
Inactivation caused a reduction of contralesional choices. Inactivation effects on fMRI
activity were anatomically and functionally specific and mainly consisted of: (i) activity
reduction in the upper bank of the superior temporal sulcus (temporal parietal occipital
area) for single contralesional targets, especially in the inactivated hemisphere; and (ii)
activity increase accompanying contralesional choices between bilateral targets in several
frontal and parieto-temporal areas in both hemispheres. There was no overactivation for
ipsilesional targets or choices in the intact hemisphere. Task-specific effects of LIP
inactivation on blood oxygen level-dependent activity in the temporal parietal occipital area
underline the importance of the superior temporal sulcus for spatial processing.
Furthermore, our results agree only partially with the influential interhemispheric
competition model of spatial neglect and suggest an additional component of
interhemispheric cooperation in the compensation of neglect deficits.