Gereon R. Fink

A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data.

Correlating the activation foci identified in functional imaging studies of the human brain with structural (e.g., cytoarchitectonic) information on the activated areas is a major methodological challenge for neuroscience research. We here present a new approach to make use of three-dimensional probabilistic cytoarchitectonic maps, as obtained from the analysis of human post-mortem brains, for correlating microscopical, anatomical and functional imaging data of the cerebral cortex. We introduce a new, MATLAB based toolbox for the SPM2 software package which enables the integration of probabilistic cytoarchitectonic maps and results of functional imaging studies. The toolbox includes the functionality for the construction of summary maps combining probability of several cortical areas by finding the most probable assignment of each voxel to one of these areas. Its main feature is to provide several measures defining the degree of correspondence between architectonic areas and functional foci. The software, together with the presently available probability maps, is available as open source software to the neuroimaging community. This new toolbox provides an easy-to-use tool for the integrated analysis of functional and anatomical data in a common reference space.

Cerebral Representation of One's Own Past: Neural Networks Involved in Autobiographical Memory

We studied the functional anatomy of affect-laden autobiographical memory in normal volunteers. Using H215O positron emission tomography (PET), we measured changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements were obtained during three conditions: REST, i.e., subjects lay at rest (for control); IMPERSONAL, i.e., subjects listened to sentences containing episodic information taken from an autobiography of a person they did not know, but which had been presented to them before PET scanning (nonautobiographical episodic memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing information taken from their own past (autobiographical episodic memory ecphory). Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory) resulted in relative rCBF increases symmetrically in both temporal lobes including the temporal poles and medial and superior temporal gyri. The same loci, however, with a stronger lateralization to the right hemisphere were activated in the comparison PERSONAL to REST (autobiographical episodic memory ecphory). In addition, the right temporomesial, right dorsal prefrontal, right posterior cingulate areas, and the left cerebellum were activated. A comparison of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic memory ecphory) demonstrated a preponderantly right hemispheric activation including primarily right temporomesial and temporolateral cortex, right posterior cingulate areas, right insula, and right prefrontal areas. The right temporomesial activation included hippocampus, parahippocampus, and amygdala. These results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.

Polymodal Motion Processing in Posterior Parietal and Premotor Cortex: A Human fMRI Study Strongly Implies Equivalencies between Humans and Monkeys

In monkeys, posterior parietal and premotor cortex play an important integrative role in polymodal motion processing. In contrast, our understanding of the convergence of senses in humans is only at its beginning. To test for equivalencies between macaque and human polymodal motion processing, we used functional MRI in normals while presenting moving visual, tactile, or auditory stimuli. Increased neural activity evoked by all three stimulus modalities was found in the depth of the intraparietal sulcus (IPS), ventral premotor, and lateral inferior postcentral cortex. The observed activations strongly suggest that polymodal motion processing in humans and monkeys is supported by equivalent areas. The activations in the depth of IPS imply that this area constitutes the human equivalent of macaque area VIP.

Neural Correlates of First-Person Perspective as One Constituent of Human Self-Consciousness

Taking the first-person perspective (1PP) centered upon ones own body as opposed to the third-person perspective (3PP), which enables us to take the viewpoint of someone else, is constitutive for human self-consciousness. At the underlying representational or cognitive level, these operations are processed in an egocentric reference frame, where locations are represented centered around another persons (3PP) or ones own perspective (1PP). To study 3PP and 1PP, both operating in egocentric frames, a virtual scene with an avatar and red balls in a room was presented from different camera viewpoints to normal volunteers (n = 11) in a functional magnetic resonance imaging experiment. The task for the subjects was to count the objects as seen either from the avatars perspective (3PP) or ones own perspective (1PP). The scene was presented either from a ground view (GV) or an aerial view (AV) to investigate the effect of view on perspective taking. The factors perspective (3PP vs. 1PP) and view (GV vs. AV) were arranged in a two-factorial way. Reaction times were increased and percent correctness scores were decreased in 3PP as opposed to 1PP. To detect the neural mechanisms associated with perspective taking, functional magnetic resonance imaging was employed. Data were analyzed using SPM99 in each subject and non-parametric statistics on the group level. Activations common to 3PP and 1PP (relative to baseline) were observed in a network of occipital, parietal, and prefrontal areas. Deactivations common to 3PP and 1PP (relative to baseline) were observed predominantly in mesial (i.e., parasagittal) cortical and lateral superior temporal areas bilaterally. Differential increases of neural activity were found in mesial superior parietal and right premotor cortex during 3PP (relative to 1PP), whereas differential increases during 1PP (relative to 3PP) were found in mesial prefrontal cortex, posterior cingulate cortex, and superior temporal cortex bilaterally. The data suggest that in addition to joint neural mechanisms, for example, due to visuospatial processing and decision making, 3PP and 1PP rely on differential neural processes. Mesial cortical areas are involved in decisional processes when the spatial task is solved from ones own viewpoint, whereas egocentric operations from another persons perspective differentially draw upon cortical areas known to be involved in spatial cognition.

Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space—The roles of Brodmann areas 44 and 45

We investigated neural activations underlying a verbal fluency task and cytoarchitectonic probabilistic maps of Brocas speech region (Brodmanns areas 44 and 45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging (fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412 (1999) 319] and developed a method to combine both data sets. In the fMRI experiment, verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from predefined categories. A factorial design was used with factors verbal class (semantic vs. overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44 and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo fMRI and postmortem MR data were warped to a common reference brain using a new elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about intersubject variability were calculated for both areas and superimposed on the functional data, which showed the involvement of left hemisphere areas with verbal fluency relative to the baseline. Semantic relative to overlearned fluency showed greater involvement of left area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so differentially. Left area 45 is more involved in semantic aspects of language processing, while area 44 is probably involved in high-level aspects of programming speech production per se. The combination of functional data analysis with a new elastic warping tool and cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved in language.

Prefrontal involvement in imitation learning of hand actions: Effects of practice and expertise

In this event-related fMRI study, we demonstrate the effects of a single session of practising configural hand actions (guitar chords) on cortical activations during observation, motor preparation and imitative execution. During the observation of non-practised actions, the mirror neuron system (MNS), consisting of inferior parietal and ventral premotor areas, was more strongly activated than for the practised actions. This finding indicates a strong role of the MNS in the early stages of imitation learning. In addition, the left dorsolateral prefrontal cortex (DLPFC) was selectively involved during observation and motor preparation of the non-practised chords. This finding confirms Buccino et al.s [Buccino, G., Vogt, S., Ritzl, A., Fink, G.R., Zilles, K., Freund, H.-J., Rizzolatti, G., 2004a. Neural circuits underlying imitation learning of hand actions: an event-related fMRI study. Neuron 42, 323-334] model of imitation learning: for actions that are not yet part of the observers motor repertoire, DLPFC engages in operations of selection and combination of existing, elementary representations in the MNS. The pattern of prefrontal activations further supports Shallices [Shallice, T., 2004. The fractionation of supervisory control. In: Gazzaniga, M.S. (Ed.), The Cognitive Neurosciences, Third edition. MIT Press, Cambridge, MA, pp. 943-956] proposal of a dominant role of the left DLPFC in modulating lower level systems and of a dominant role of the right DLPFC in monitoring operations.

The Neural Basis of Vertical and Horizontal Line Bisection Judgments: An fMRI Study of Normal Volunteers

Bisection of horizontal lines is used as a clinical test of spatial cognition in patients with left visuospatial neglect after right hemisphere lesions. Bisection of vertical lines has also been employed, albeit less frequently. Interestingly, normal subjects often bisect horizontal lines too far left and vertical lines too high. We used fMRI to investigate whether vertical/horizontal stimulus orientation interacts with the neural mechanisms associated with line bisection judgments (the Landmark task). For control of orientation per se, subjects performed a visual detection task with the same stimuli. Statistical analysis of evoked BOLD responses employed SPM99. The Landmark task increased neural activity (P < 0.05, corrected) in the superior and inferior parietal lobes bilaterally, though predominantly on the right; early visual processing areas bilaterally; and cerebellar vermis, left cerebellar hemisphere, anterior cingulate, and prefrontal cortex bilaterally. Vertical lines (relative to horizontal lines and vice versa) increased neural activity in early visual processing areas, consistent with differential retinotopic stimulation. In addition, vertical lines activated right parietooccipital and superior posterior parietal cortex bilaterally. No significant interactions between the neural mechanisms associated with task and stimuli were observed. Increased neural activation in parietal and parietooccipital cortex associated with vertical lines may reflect increased attentional demands associated with this stimulus orientation. The right hemispheric dominance observed in posterior parietal during the Landmark task irrespective of stimulus orientation is consistent with lesion studies. Our results suggest that the behavioral patterns observed in normal subjects and neurological patients result from different stimulus effects rather than differential task demands.

Space Coding in Primate Posterior Parietal Cortex

Neuropsychological studies of patients with lesions of right frontal (premotor) or posterior parietal cortex often show severe impairments of attentive sensorimotor behavior. Such patients frequently manifest symptoms like hemispatial neglect or extinction. Interestingly, these behavioral deficits occur across different sensory modalities and are often organized in head- or body-centered coordinates. These neuropsychological data provide evidence for the existence of a network of polymodal areas in (primate) premotor and inferior parietal cortex representing visual spatial information in a nonretinocentric frame of reference. In the monkey, a highly modular structural and functional specialization has been demonstrated especially within posterior parietal cortex. One such functionally specialized area is the ventral intraparietal area (VIP). This area is located in the fundus of the intraparietal sulcus and contains many neurons that show polymodal directionally selective discharges, i.e., these neurons respond to moving visual, tactile, vestibular, or auditory stimuli. Many of these neurons also encode sensory information from different modalities in a common, probably head-centered, frame of reference. Functional imaging data on humans reveal a network of cortical areas that respond to polymodal stimuli conveying motion information. One of these regions of activation is located in the depth of human intraparietal sulcus. Accordingly, it is suggested that this area constitutes the human equivalent of monkey area VIP. The functional role of area VIP for polymodal spatial perception in normals as well as the functional implications of lesions of area VIP in parietal patients needs to be established in further experiments.

Performing allocentric visuospatial judgments with induced distortion of the egocentric reference frame: an fMRI study with clinical implications.

The temporary improvement of visuospatial neglect during galvanic vestibular stimulation (Scand. J. Rehabil. Med. 31 (1999)117) may result from correction of the spatial reference frame distorted by the responsible lesion. Prior to an investigation of the neural basis of this effect in neurological patients, exploration of the neural mechanisms underlying such procedures in normals is required to provide insight into the physiological basis thereof. Despite their clinical impact, the neural mechanisms underlying the interaction of galvanic (and other) vestibular manipulations with visuospatial processing (and indeed the neural bases of how spatial reference frames are computed in man) remain to be clarified. We accordingly used fMRI in normal volunteers to investigate the effect of galvanically induced interference with the egocentric spatial reference frame on the neural processes underlying allocentric visuospatial (line bisection) judgments. A significant specific interaction of galvanic vestibular stimulation with the neural mechanisms underlying allocentric visuospatial judgments was observed in right posterior parietal and ventral premotor cortex only. Activation of these areas previously found to be damaged in visuospatial neglect suggests that these effects reflect the increased processing demands when compensating for the distorted egocentric spatial reference frame while maintaining accurate performance during the allocentric spatial task. These results thus implicate right posterior parietal and right ventral premotor cortex in the computation of spatial reference frames. Furthermore, our data imply a specific physiological basis for the temporary improvement of visuospatial neglect in patients with right hemisphere lesions during galvanic vestibular stimulation and may thus impact upon the rehabilitation of neglect: understanding the interaction of galvanic vestibular stimulation with allocentric visuospatial judgments in healthy volunteers may lead to the more effective deployment of such techniques in neurological patients.

Cortical Representations of Personally Familiar Objects and Places: Functional Organization of the Human Posterior Cingulate Cortex

The recognition of both personally familiar objects and places involves nonspatial memory retrieval processes, but only personally familiar places are represented as space. Although the posterior cingulate cortex (PCC) is considered to process both types of such memories, its functional organization is poorly understood. In this event-related fMRI study, normal subjects judged familiar/unfamiliar pictures in four categories: familiar places (FP), familiar objects (FO), unfamiliar places (UP), and unfamiliar objects (UO), thus constituting a two-factorial design. A significant main effect of stimuli with greater activation in the place (FP and UP) than object (FO and UO) trials was observed bilaterally in several medial temporo-occipito-parietal regions, including the caudal PCC (cPCC) and parahippocampal gyrus. The reverse comparison revealed greater activation in the lateral inferior occipito-temporal junctions and intraparietal sulci bilaterally. A significant main effect of familiarity with greater activation in the familiar (FP and FO) than unfamiliar (UP and UO) trials was observed in the mid-dorsal PCC (mPCC), retrosplenial cortex, posterior precuneus, and the left intraparietal sulcus. Activation specific to the FP trials (as assessed by the interaction) was observed in the right posterodorsal PCC (pPCC) only. Together with data from previous functional imaging studies, the results suggest a functional segregation of human PCC with differential involvement of pPCC in spatial representations of personally familiar places and of the mPCC and retrosplenial cortex in episodic retrieval of personally familiar places and objects. Activation of the left intraparietal sulcus may reflect retrieval of memories related to object manipulation.