The dorsal mesial frontal cortex contains the supplementary motor area (SMA) and the pre-supplementary motor area (pre-SMA), which play an important role in action and cognition. Evidence from cytoarchitectonic, stimulation, and functional studies suggests structural and functional divergence between the two subregions. However, a microstructural map of these areas obtained in a representative sample of brains in a stereotaxic reference space is still lacking. In the present study we show that the dorsal mesial frontal motor cortex comprises two microstructurally different brain regions: area SMA and area pre-SMA. Area-specific cytoarchitectonic patterns were studied in serial histological sections stained for cell bodies of ten human postmortem brains. Borders of the two cortical areas were identified using image analysis and statistical features. The 3D reconstructed areas were transferred to a common reference space, and probabilistic maps were calculated by superimposing the individual maps. A coordinate-based meta-analysis of functional imaging data was subsequently performed using the two probabilistic maps as microstructurally defined seed regions. It revealed that areas SMA and pre-SMA were strongly co-activated with areas in precentral, supramarginal and superior frontal gyri, Rolandic operculum, thalamus, putamen and cerebellum. Both areas were related to motor functions, but area pre-SMA was involved in more complex processes such as learning, cognitive processes and perception. The here described subsequent analyses led to converging evidence supporting the microstructural, and functional segregation of areas SMA and pre-SMA, and maps will be made available to the scientific community to further elucidate the microstructural substrates of motor and cognitive control.
The aim of this study was to provide a computational system model of effective connectivity in the human brain underlying overt speech production. Meta-analysis of neuroimaging studies and functional magnetic resonance imaging data acquired during a verbal fluency task revealed a core network consisting of Brodmann's area (BA) 44 in Broca's region, anterior insula, basal ganglia, cerebellum, premotor cortex (PMC, BA 6) and primary motor cortex (M1, areas 4a/4p). Dynamic causal modelling (DCM) indicated the highest evidence for a system architecture featuring the insula in a serial position between BA 44 and two parallel nodes (cerebellum/basal ganglia), from which information converges onto the PMC and finally M1. Parameter inference revealed that effective connectivity from the insular relay into the cerebellum/basal ganglia is primarily task driven (preparation) while the output into the cortical motor system strongly depends on the actual word production rate (execution). DCM hence allowed not only a quantitative characterization of the human speech production network, but also the distinction of a preparatory and an executive subsystem within it. The proposed model of physiological integration during speech production may now serve as a reference for investigations into the neurobiology of pathological states such as dysarthria and apraxia of speech.
In language production, naming a picture with a gender-marked determiner phrase is faster in the presence of a distractor noun with the same grammatical gender (congruent condition) as compared with a different grammatical gender (incongruent condition). We investigated the neural correlates of this determiner congruency effect in German with functional magnetic resonance imaging (fMRI). Participants named pictures of real objects with determiner phrases (e.g. "der Tisch"-the table) in the presence of a gender-congruent or gender-incongruent distractor noun. Different comparisons allow the following functional segregation within the prefrontal cortex. First, the comparison between picture naming versus rest revealed a steeper slope of the haemodynamic response function (HRF) in the gender-congruent than the gender-incongruent condition in the left BA 44, suggesting the involvement of BA 44 in determiner selection. HRF amplitude differences between the congruent and the incongruent condition were observed outside the language network in the right fronto-median wall (congruent > incongruent), and in the left premotor cortex, middle frontal gyrus, cerebellum, and inferior parietal lobe (incongruent > congruent). The latter regions are known to be involved in the processing of incongruence and conflict in general. The data thus reveal the involvement of the left BA 44 in the selection of determiners for language production.
Age-related differences in the anatomical structure of the brains from 51 healthy male subjects (age: 18-51 years) were analyzed by deformation field morphometry in a cross-sectional study. The magnetic resonance images of the brains were nonlinearly registered onto the image of a reference brain: the registration algorithm simulated an elastic deformation of each brain (source brain) so that the voxelwise intensity differences with the reference brain were minimized. A three-dimensional deformation field was calculated for each source brain that encoded the anatomical differences between the source brain and the reference brain. Maps of voxelwise volume differences between each subject's brain and the reference brain were analyzed. They showed age-related differences in anatomically defined regions of interest. Major volume decreases were found in the white matter and nuclei of the cerebellum, as well as in the ventral thalamic nuclei and the somatosensory and motor cortices, including the underlying white matter. These findings suggest that aging between the second and sixth decade predominantly affects subcortical nuclei and cortical areas of the sensorimotor system, forming the cortico-rubro-cerebello-thalamo-cortical pathway. Additionally, a pronounced age-related decline in volume was observed in the rostral anterior cingulate, orbitofrontal, and lateral prefrontal cortices. Almost no differences were observed in the occipital and temporal lobes. The ventricles showed a pronounced widening. Remarkably, these volume differences occur at a relatively early period of the human life span. It may be speculated that these structural differences accompany or precede differences in sensorimotor functions and behavior.
The cerebellar nuclei are involved in several brain functions, including the modulation of motor and cognitive performance. To differentiate their participation in these functions, and to analyze their changes in neurodegenerative and other diseases as revealed by neuroimaging, stereotaxic maps are necessary. These maps reflect the complex spatial structure of cerebellar nuclei with adequate spatial resolution and detail. Here we report on the cytoarchitecture of the dentate, interposed (emboliform and globose) and fastigial nuclei, and introduce 3D probability maps in stereotaxic MNI-Colin27 space as a prerequisite for subsequent meta-analysis of their functional involvement. Histological sections of 10 human post mortem brains were therefore examined. Differences in cell density were measured and used to distinguish a dorsal from a ventral part of the dentate nucleus. Probabilistic maps were calculated, which indicate the position and extent of the nuclei in 3D-space, while considering their intersubject variability. The maps of the interposed and the dentate nuclei differed with respect to their interaction patterns and functions based on meta-analytic connectivity modeling and quantitative functional decoding, respectively. For the dentate nucleus, significant (p < 0.05) co-activations were observed with thalamus, supplementary motor area (SMA), putamen, BA 44 of Broca's region, areas of superior and inferior parietal cortex, and the superior frontal gyrus (SFG). In contrast, the interposed nucleus showed more limited co-activations with SMA, area 44, putamen, and SFG. Thus, the new stereotaxic maps contribute to analyze structure and function of the cerebellum. These maps can be used for anatomically reliable and precise identification of degenerative alteration in MRI-data of patients who suffer from various cerebellar diseases.
Although it is well established that there is cognitive dysfunction in spinocerebellar ataxia type 3 (SCA3), it is unknown whether cognition deteriorates with disease progression. We therefore prospectively studied cognitive function in patients with SCA3. Eleven patients with SCA3 were assessed using an extensive neuropsychological test battery and retested after 3.5 ± 0.4 years. In addition to ataxia and motor control, verbal learning and verbal and figural memory deteriorated significantly during the follow-up period. An increase in depressive symptoms was not observed. The observation that memory and learning abilities deteriorated with disease progression suggests that cognitive dysfunction is an integral part of SCA3. Because the applied tests for memory function did not require motor responses, cognitive decline cannot be attributed to progressive cerebellar ataxia. The deterioration of verbal and figural memory can be explained either by extracerebellar pathology or by disruption of cerebellar-cerebral circuitries.
There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech.
Recent neuroimaging studies make contradictory predictions about the involvement of left Brodmann's area (BA) 44 in processing local syntactic violations in determiner phrases (DPs). Some studies suggest a role for BA 44 in detecting local syntactic violations, whereas others attribute this function to the left premotor cortex. Therefore, the present event-related functional magnetic resonance imaging (fMRI) study investigated whether left-cytoarchitectonic BA 44 was activated when German DPs involving syntactic gender violations were compared with correct DPs (correct: 'der Baum'-the[masculine] tree[masculine]; violated: 'das Baum'--the[neuter] tree[masculine]). Grammaticality judgements were made for both visual and auditory DPs to be able to generalize the results across modalities. Grammaticality judgements involved, among others, left BA 44 and left BA 6 in the premotor cortex for visual and auditory stimuli. Most importantly, activation in left BA 44 was consistently higher for violated than for correct DPs. This finding was behaviourally corroborated by longer reaction times for violated versus correct DPs. Additional brain regions, showing the same effect, included left premotor cortex, supplementary motor area, right middle and superior frontal cortex, and left cerebellum. Based on earlier findings from the literature, the results indicate the involvement of left BA 44 in processing local syntactic violations when these include morphological features, whereas left premotor cortex seems crucial for the detection of local word category violations.
Anatomical global spatial normalization (aGSN) is presented as a method to scale high-resolution brain images to control for variability in brain size without altering the mean size of other brain structures. Two types of mean preserving scaling methods were investigated, "shape preserving" and "shape standardizing". aGSN was tested by examining 56 brain structures from an adult brain atlas of 40 individuals (LPBA40) before and after normalization, with detailed analyses of cerebral hemispheres, all gyri collectively, cerebellum, brainstem, and left and right caudate, putamen, and hippocampus. Mean sizes of brain structures as measured by volume, distance, and area were preserved and variance reduced for both types of scale factors. An interesting finding was that scale factors derived from each of the ten brain structures were also mean preserving. However, variance was best reduced using whole brain hemispheres as the reference structure, and this reduction was related to its high average correlation with other brain structures. The fractional reduction in variance of structure volumes was directly related to ρ (2), the square of the reference-to-structure correlation coefficient. The average reduction in variance in volumes by aGSN with whole brain hemispheres as the reference structure was approximately 32%. An analytical method was provided to directly convert between conventional and aGSN scale factors to support adaptation of aGSN to popular spatial normalization software packages.