Ronald Peeters

Neural Basis of Aging: The Penetration of Cognition into Action Control

Although functional imaging studies have frequently examined age-related changes in neural recruitment during cognitive tasks, much less is known about such changes during motor performance. In the present study, we used functional magnetic resonance imaging to investigate age-related changes in cyclical hand and/or foot movements across different degrees of complexity. Right-handed volunteers (11 young, 10 old) were scanned while performing isolated flexion-extension movements of the right wrist and foot as well as their coordination, according to the “easy” isodirectional and “difficult” nonisodirectional mode. Findings revealed activation of a typical motor network in both age groups, but several additional brain areas were involved in the elderly. Regardless of the performed motor task, the elderly exhibited additional activation in areas involved in sensory processing and integration, such as contralateral anterior insula, frontal operculum, superior temporal gyrus, supramarginal gyrus, secondary somatosensory area, and ipsilateral precuneus. Age-related activation differences during coordination of both segments were additionally observed in areas reflecting increased cognitive monitoring of motor performance, such as the pre-supplementary motor area, pre-dorsal premotor area, rostral cingulate, and prefrontal cortex. In the most complex coordination task, the elderly exhibited additional activation in anterior rostral cingulate and dorsolateral prefrontal cortex, known to be involved in suppression of prepotent response tendencies and inhibitory cognitive control. Overall, these findings are indicative of an age-related shift along the continuum from automatic to more controlled processing of movement. This increased cognitive monitoring of movement refers to enhanced attentional deployment, more pronounced processing of sensory information, and intersensory integration.

The Representation of Tool Use in Humans and Monkeys: Common and Uniquely Human Features

Though other species of primates also use tools, humans appear unique in their capacity to understand the causal relationship between tools and the result of their use. In a comparative fMRI study, we scanned a large cohort of human volunteers and untrained monkeys, as well as two monkeys trained to use tools, while they observed hand actions and actions performed using simple tools. In both species, the observation of an action, regardless of how performed, activated occipitotemporal, intraparietal, and ventral premotor cortex, bilaterally. In humans, the observation of actions done with simple tools yielded an additional, specific activation of a rostral sector of the left inferior parietal lobule (IPL). This latter site was considered human-specific, as it was not observed in monkey IPL for any of the tool videos presented, even after monkeys had become proficient in using a rake or pliers through extensive training. In conclusion, while the observation of a grasping hand activated similar regions in humans and monkeys, an additional specific sector of IPL devoted to tool use has evolved in Homo sapiens, although tool-specific neurons might reside in the monkey grasping regions. These results shed new light on the changes of the hominid brain during evolution.

Longitudinal Assessment of Chemotherapy-Induced Structural Changes in Cerebral White Matter and Its Correlation With Impaired Cognitive Functioning

PURPOSE To uncover the neural substrate of cognitive impairment related to adjuvant chemotherapy, we studied cerebral white matter (WM) integrity before and after chemotherapy by using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment. PATIENTS AND METHODS Thirty-four young premenopausal women with early-stage breast cancer who were exposed to chemotherapy underwent neuropsychologic testing and DTI before the start of chemotherapy (t1) and 3 to 4 months after treatment (t2). Sixteen patients not exposed to chemotherapy and 19 age-matched healthy controls underwent the same assessment at matched intervals. In all groups, we used paired t tests to study changes in neuropsychologic test scores and whole-brain voxel-based paired t tests to study changes in WM fractional anisotropy (FA; a DTI measure that reflects WM tissue organization), with depression scores and intelligence quotient as included covariates. We correlated changes of neuropsychologic test scores with the mean change of FA for regions that survived the paired t tests in patients treated with chemotherapy. RESULTS In contrast to controls, the chemotherapy-treated group performed significantly worse on attention tests, psychomotor speed, and memory at t2 compared with t1 (P < .05). In the chemotherapy-treated group, we found significant decreases of FA in frontal, parietal, and occipital WM tracts after treatment (familywise error P < .05), whereas for both control groups, FA values were the same between t1 and t2. Furthermore, performance changes in attention and verbal memory correlated with mean regional FA changes in chemotherapy-treated patients (P < .05). CONCLUSION We report evidence of longitudinal changes in cognitive functioning and cerebral WM integrity after chemotherapy as well as an association between both.

The Retinotopic Organization of the Human Middle Temporal Area MT/V5 and Its Cortical Neighbors

Although there is general agreement that the human middle temporal (MT)/V5+ complex corresponds to monkey area MT/V5 proper plus a number of neighboring motion-sensitive areas, the identification of human MT/V5 within the complex has proven difficult. Here, we have used functional magnetic resonance imaging and the retinotopic mapping technique, which has very recently disclosed the organization of the visual field maps within the monkey MT/V5 cluster. We observed a retinotopic organization in humans very similar to that documented in monkeys: an MT/V5 cluster that includes areas MT/V5, pMSTv (putative ventral part of the medial superior temporal area), pFST (putative fundus of the superior temporal area), and pV4t (putative V4 transitional zone), and neighbors a more ventral putative human posterior inferior temporal area (phPIT) cluster. The four areas in the MT/V5 cluster and the two areas in the phPIT cluster each represent the complete contralateral hemifield. The complete MT/V5 cluster comprises 70% of the motion localizer activation. Human MT/V5 is located in the region bound by lateral, anterior, and inferior occipital sulci and occupies only one-fifth of the motion complex. It shares the basic functional properties of its monkey homolog: receptive field size relative to other areas, response to moving and static stimuli, as well as sensitivity to three-dimensional structure from motion. Functional properties sharply distinguish the MT/V5 cluster from its immediate neighbors in the phPIT cluster and the LO (lateral occipital) regions. Together with similarities in retinotopic organization and topological neighborhood, the functional properties suggest that MT/V5 in human and macaque cortex are homologous.

Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis

OBJECTIVE Aim of present study was to evaluate changes in diffusion tensor imaging (DTI) parameters in the whole brain of 28 patients with amyotrophic lateral sclerosis (ALS) compared to 26 healthy controls. METHODS In both fibertracking and voxel-based analysis, quantitative comparisons of the diffusion parameters between ALS patients and controls were performed. Correlation analyses of diffusion parameters and disease duration and disease severity were performed. A second DTI examination was acquired, allowing the evaluation of the effect of disease progression on the diffusion parameters. RESULTS Fibertracking analysis revealed that especially the precentral part of the corticospinal tract (CST) was impaired. In the voxel-based analysis, it was shown that changes of diffusion parameters occurred throughout the brain, including frontal, temporal and parietal lobes. Disease severity was inversely correlated with the fractional anisotropy (FA). In the follow-up examination, a further decline of FA over time could be demonstrated in the CST as well as in the whole brain white matter. INTERPRETATION This study provides support for the view of ALS as being a multisystem degenerative disease, in which abnormalities of extra-motor areas play an important role in the in vivo physiopathology.

Gliomas: Diffusion Kurtosis MR Imaging in Grading

PURPOSE To assess the diagnostic accuracy of diffusion kurtosis magnetic resonance imaging parameters in grading gliomas. MATERIALS AND METHODS The institutional review board approved this prospective study, and informed consent was obtained from all patients. Diffusion parameters-mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis, and radial and axial kurtosis-were compared in the solid parts of 17 high-grade gliomas and 11 low-grade gliomas (P<.05 significance level, Mann-Whitney-Wilcoxon test, Bonferroni correction). MD, FA, mean kurtosis, radial kurtosis, and axial kurtosis in solid tumors were also normalized to the corresponding values in contralateral normal-appearing white matter (NAWM) and the contralateral posterior limb of the internal capsule (PLIC) after age correction and were compared among tumor grades. RESULTS Mean, radial, and axial kurtosis were significantly higher in high-grade gliomas than in low-grade gliomas (P = .02, P = .015, and P = .01, respectively). FA and MD did not significantly differ between glioma grades. All values, except for axial kurtosis, that were normalized to the values in the contralateral NAWM were significantly different between high-grade and low-grade gliomas (mean kurtosis, P = .02; radial kurtosis, P = .03; FA, P = .025; and MD, P = .03). When values were normalized to those in the contralateral PLIC, none of the considered parameters showed significant differences between high-grade and low-grade gliomas. The highest sensitivity and specificity for discriminating between high-grade and low-grade gliomas were found for mean kurtosis (71% and 82%, respectively) and mean kurtosis normalized to the value in the contralateral NAWM (100% and 73%, respectively). Optimal thresholds for mean kurtosis and mean kurtosis normalized to the value in the contralateral NAWM for differentiating high-grade from low-grade gliomas were 0.52 and 0.51, respectively. CONCLUSION There were significant differences in kurtosis parameters between high-grade and low-grade gliomas; hence, better separation was achieved with these parameters than with conventional diffusion imaging parameters.

The processing of three-dimensional shape from disparity in the human brain.

Three-dimensional (3D) shape is important for the visual control of grasping and manipulation and for object recognition. Although there has been some progress in our understanding of how 3D shape is extracted from motion and other monocular cues, little is known of how the human brain extracts 3D shape from disparity, commonly regarded as the strongest depth cue. Previous fMRI studies in the awake monkey have established that the interaction between stereo (present or absent) and the order of disparity (zero or second order) constitutes the MR signature of regions housing second-order disparity-selective neurons (Janssen et al., 2000; Srivastava et al., 2006; Durand et al., 2007; Joly et al., 2007). Testing the interaction between stereo and order of disparity in a large cohort of human subjects, revealed the involvement of five IPS regions (VIPS/V7*, POIPS, DIPSM, DIPSA, and phAIP), as well as V3 and the V3A complex in occipital cortex, the posterior inferior temporal gyrus (ITG), and ventral premotor cortex (vPrCS) in the extraction and processing of 3D shape from stereo. Control experiments ruled out attention and convergence eye movements as confounding factors. Many of these regions, DIPSM, DIPSA, phAIP, and probably posterior ITG and ventral premotor cortex, correspond to monkey regions with similar functionality, whereas the evolutionarily new or modified regions are located in occipital (the V3A complex) and occipitoparietal cortex (VIPS/V7* and POIPS). Interestingly, activity in these occipital regions correlates with the depth amplitude perceived by the subjects in the 3D surfaces used as stimuli in these fMRI experiments.

Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis: Revisited

Voxel‐based analyses (VBA) are increasingly being used to detect white matter abnormalities with diffusion tensor imaging (DTI) in different types of pathologies. However, the validity, specificity, and sensitivity of statistical inferences of group differences to a large extent depend on the quality of the spatial normalization of the DTI images. Using high‐dimensional nonrigid coregistration techniques that are able to align both the spatial and orientational diffusion information and incorporate appropriate templates that contain this complete DT information may improve this quality. Alternatively, a hybrid technique such as tract‐based spatial statistics (TBSS) may improve the reliability of the statistical results by generating voxel‐wise statistics without the need for perfect image alignment and spatial smoothing. In this study, we have used (1) a coregistration algorithm that was optimized for coregistration of DTI data and (2) a population‐based DTI atlas to reanalyze our previously published VBA, which compared the fractional anisotropy and mean diffusivity maps of patients with amyotrophic lateral sclerosis (ALS) with those of healthy controls. Additionally, we performed a complementary TBSS analysis to improve our understanding and interpretation of the VBA results. We demonstrate that, as the overall variance of the diffusion properties is lowered after normalizing the DTI data with such recently developed techniques (VBA using our own optimized high‐dimensional nonrigid coregistration and TBSS), more reliable voxel‐wise statistical results can be obtained than had previously been possible, with our VBA and TBSS yielding very similar results. This study provides support for the view of ALS as a multisystem disease, in which the entire frontotemporal lobe is implicated. Hum Brain Mapp, 2009.

Amygdala hyperfunction in phobic fear normalizes after exposure

BACKGROUND The amygdala is implicated as a key brain structure in fear processing. Studies exploring this process using the paradigm of fear conditioning have implicated the amygdala in fear acquisition and in generating behavioral fear responses. As such, fear extinction could be expected to induce a reduction in amygdala activity. However, exposure in specific phobia has never been shown persistently to reduce amygdala activity. METHODS By means of event-related functional magnetic resonance imaging, responses to phobia-related, general threat, and neutral pictures were measured before and 2 weeks after an intensive exposure session in 20 subjects with specific phobia for spiders and compared with healthy control subjects. RESULTS Phobic subjects showed increased amygdala activity at baseline. This hyperactivity was significantly reduced 2 weeks after exposure therapy. Furthermore, a significant reduction of hyperactivity in anterior cingulate cortex and insula was found postexposure. CONCLUSIONS To our knowledge, this is the first study demonstrating the effect of exposure on the amygdala in specific phobia. Our findings suggest that exposure therapy can have an effect on subcortical structures.

Parietal regions processing visual 3D shape extracted from disparity

Three-dimensional (3D) shape is important for the visual control of grasping and manipulation. We used fMRI to study the processing of 3D shape extracted from disparity in human parietal cortex. Subjects stereoscopically viewed random-line stimuli portraying a 3D structure, a 2D structure in multiple depth planes or a 2D structure in the fixation plane. Subtracting the second from the first condition yields depth-structure sensitive regions and subtracting the third from the second position-in-depth sensitive regions. Two anterior intraparietal sulcus (IPS) regions, the dorsal IPS medial (DIPSM) and the dorsal IPS anterior (DIPSA) regions, were sensitive to depth structure and not to position in depth, while a posterior IPS region, the ventral IPS (VIPS) region, had a mixed sensitivity. All three IPS regions were also sensitive to 2D shape, indicating that they carry full 3D shape information. Finally DIPSM, but not DIPSA was sensitive to a saccade-related task. These results underscore the importance of anterior IPS regions in the processing of 3D shape, in agreement with their proximity to grasping-related regions. Moreover, comparison with the results of Durand, J.B., Nelissen, K., Joly, O., Wardak, C., Todd, J.T., Norman, J.F., Janssen, P., Vanduffel, W., Orban, G.A., 2007. Anterior Regions of Monkey Parietal Cortex Process Visual 3D Shape. Neuron 55, 493-505 obtained in the monkey indicates that DIPSA and DIPSM may represent human homologues for the posterior part of AIP and the adjoining part of LIP respectively.