Cytoarchitectonic Areas Research Articles

Mapping of Broca's region using repetitive transcranial magnetic stimulation in correlation to functional and structural imaging

Objective: Broca's area in the left hemisphere is macro-anatomically defined by the pars opercularis and the pars triangularis of the inferior frontal gyrus, represented in cytoarchitectonic Area 44 and Area 45 respectively. Beyond speech production in general, Broca's area is supposed to be linked to differentiated functional roles in language processing. The objective of our study is to combine complementary data from functional and structural-anatomical imaging with the electrophysiological method of transcranial magnetic stimulation (TMS) in order to individually map the Broca's region within the speech network. The background idea is to identify the functionally mandatory proportions of Broca's region which is a prerequisite in neurosurgical tumor resection. In analogy to electrical brain stimulation in awake surgery, the so called “virtual lesion technique” TMS allows for inducing an acute and exhaustive reversible dysfunction without structural damage and thus directly identifies cortical areas involved in language processing. Therefore, it is an elegant method to enable for causative evidence, which vice versa complement imaging data.

Cortico-cortical connections of areas 44 and 45B in the macaque monkey

In the human brain, areas 44 and 45 constitute Broca’s region, the ventrolateral frontal region critical for language production. The homologues of these areas in the macaque monkey brain have been established by direct cytoarchitectonic comparison with the human brain. The cortical areas that project monosynaptically to areas 44 and 45B in the macaque monkey brain require clarification. Fluorescent retrograde tracers were placed in cytoarchitectonic areas 44 and 45B of the macaque monkey, as well as in the anterior part of the inferior parietal lobule and the superior temporal gyrus. The results demonstrate that ipsilateral afferent connections of area 44 arise from local frontal areas, including rostral premotor cortical area 6, from secondary somatosensory cortex, the caudal insula, and the cingulate motor region. Area 44 is strongly linked with the anterior inferior parietal lobule (particularly area PFG and the adjacent anterior intraparietal sulcus). Input from the temporal lobe is limited to the fundus of the superior temporal sulcus extending caudal to the central sulcus. There is also input from the sulcal part of area Tpt in the upper bank of the superior temporal sulcus. Area 45B shares some of the connections of area 44, but can be distinguished from area 44 by input from the caudal inferior parietal lobule (area PG) and significant input from the part of the superior temporal sulcus that extends anterior to the central sulcus. Area 45B also receives input from visual association cortex that is not observed in area 44. The results have provided a clarification of the relative connections of areas 44 and 45B of the ventrolateral frontal region which, in the human brain, subserves certain aspects of language processing.

Comparative neuroanatomical parcellation of the human and nonhuman primate temporal pole

The temporal pole is unique to nonhuman and human primates, although other species also present temporal cortex. A clear distinction is made between the gross anatomical, macroscopic temporal pole, located at the tip of the temporal lobe, and the temporal polar cortex, which is a general term that encompasses all reported divisions and can be applied to both nonhuman and human primates. In the 19th century early neuroanatomists identified the temporal polar cortex as a different entity, independent from the remainder of the temporal lobe. More recently, the temporal polar cortex has been subdivided into different fields. The analysis of the different portions that make up the temporal polar cortex was first described in the nonhuman primate, and later on in humans. In this review we examine the historical course of the concepts about the extension, structure, and main cytoarchitectonic areas. The different descriptions are presented in chronological order and their relevance is discussed. In general, some common features arise in nonhuman and human primates temporopolar cortex, namely, an increased thickness of this cortical area, a predominant dysgranular type of cortex, and a more restricted extension in humans relative to earlier accounts. A common pattern of cytoarchitectonic areas results from the criteria of previous authors, although the sulcal anatomy of the human temporal pole has great variability. The understanding of the extension, composition, and limits of the temporal polar cortex is crucial for identification of separate regions in neuroimaging studies. J. Comp. Neurol. 521:4163-4176, 2013. © 2013 Wiley Periodicals, Inc.

Distinct Parietal and Temporal Connectivity Profiles of Ventrolateral Frontal Areas Involved in Language Production

Broca's region, which in the language-dominant hemisphere of the human brain plays a major role in language production, includes two distinct cytoarchitectonic areas: 44 and 45. The unique connectivity patterns of these two areas have not been well established. In a resting-state functional connectivity study, we tested predictions about these areas from invasive tract-tracing studies of the connectivity of their homologs in the macaque monkey. We demonstrated their distinct connectivity profiles as well as their differences from the caudally adjacent ventral parts of the premotor cortex and the primary motor cortical region that represent the orofacial musculature. Area 45 is strongly connected with the superior temporal sulcus and the cortex on the adjacent superior and middle temporal gyri. In the parietal region, area 45 is connected with the angular gyrus, whereas area 44 is connected with the supramarginal gyrus. The primary motor cortical region in the caudal precentral gyrus is not connected with the posterior parietal region, which lies outside the confines of the postcentral gyrus, whereas the ventrorostral premotor cortical area 6VR, in the most anterior part of the precentral gyrus, has strong connections with the rostral supramarginal gyrus. Thus, area 44, which has stronger connections to the posterior supramarginal gyrus, can be distinguished from both the adjacent area 6VR and area 45. These findings provide a major improvement in understanding the connectivity of the areas in the ventrolateral frontal region that are involved in language production.

Functional characterization and differential coactivation patterns of two cytoarchitectonic visual areas on the human posterior fusiform gyrus

The ventral stream of the human extrastriate visual cortex shows a considerable functional heterogeneity from early visual processing (posterior) to higher, domain-specific processing (anterior). The fusiform gyrus hosts several of those "high-level" functional areas. We recently found a subdivision of the posterior fusiform gyrus on the microstructural level, that is, two distinct cytoarchitectonic areas, FG1 and FG2 (Caspers et al., Brain Structure & Function, 2013). To gain a first insight in the function of these two areas, here we studied their behavioral involvement and coactivation patterns by means of meta-analytic connectivity modeling based on the BrainMap database (www.brainmap.org), using probabilistic maps of these areas as seed regions. The coactivation patterns of the areas support the concept of a common involvement in a core network subserving different cognitive tasks, that is, object recognition, visual language perception, or visual attention. In addition, the analysis supports the previous cytoarchitectonic parcellation, indicating that FG1 appears as a transitional area between early and higher visual cortex and FG2 as a higher-order one. The latter area is furthermore lateralized, as it shows strong relations to the visual language processing system in the left hemisphere, while its right side is stronger associated with face selective regions. These findings indicate that functional lateralization of area FG2 relies on a different pattern of connectivity rather than side-specific cytoarchitectonic features.

Interoceptive and multimodal functions of the operculo-insular cortex: Tactile, nociceptive and vestibular representations

The operculo-insular cortex has been termed the ‘homeostatic control center’ or ‘general magnitude estimator’ of the human mind. In this study, somatosensory, nociceptive and caloric vestibular stimuli were applied to reveal, whether there are mainly common, or possibly specific regions activated by one modality alone and whether lateralization effects, time pattern differences or influences of the aversive nature of the stimuli could be observed.Activation of the dorsal posterior insula was caused by all stimuli alike thus terming this area multimodal. Early phases of the noxious heat and caloric vestibular stimulation led to responses in the anterior insula. Using conjunction analyses we found that left- and right-sided tactile stimulation, but not nociceptive stimulation, caused a joint activation of the cytoarchitectonic area OP1 and nociceptive but not tactile stimulation of the anterior insula bilaterally. Tactile activation in the parietal operculum (SII, OP1) was distinct from nociceptive activation (OP3 and frontal operculum).The joint activation by all three stimuli located in the dorsal posterior insula argues for the presence of multisensory structures. The distinct activation of the anterior insula by aversive stimuli and the posterior insula by multisensory signals supports the concept of a partitioned insular cortex recently introduced based on connectivity studies and meta-analyses.

Tackling the multifunctional nature of Broca's region meta-analytically: Co-activation-based parcellation of area 44

Cytoarchitectonic area 44 of Broca's region in the left inferior frontal gyrus is known to be involved in several functional domains including language, action and music processing. We investigated whether this functional heterogeneity is reflected in distinct modules within cytoarchitectonically defined left area 44 using meta-analytic connectivity-based parcellation (CBP). This method relies on identifying the whole-brain co-activation pattern for each area 44 voxel across a wide range of functional neuroimaging experiments and subsequently grouping the voxels into distinct clusters based on the similarity of their co-activation patterns. This CBP analysis revealed that five separate clusters exist within left area 44. A post-hoc functional characterization and functional connectivity analysis of these five clusters was then performed. The two posterior clusters were primarily associated with action processes, in particular with phonology and overt speech (posterior-dorsal cluster) and with rhythmic sequencing (posterior-ventral cluster). The three anterior clusters were primarily associated with language and cognition, in particular with working memory (anterior-dorsal cluster), with detection of meaning (anterior-ventral cluster) and with task switching/cognitive control (inferior frontal junction cluster). These five clusters furthermore showed specific and distinct connectivity patterns. The results demonstrate that left area 44 is heterogeneous, thus supporting anatomical data on the molecular architecture of this region, and provide a basis for more specific interpretations of activations localized in area 44.

Functional activation during reading in relation to the sulci of the angular gyrus region

Neurological studies suggest that the angular gyrus region of the inferior parietal lobule may be critical for reading. However, unambiguous demonstration of angular gyrus involvement from lesion and functional neuroimaging studies is lacking, partly because of the absence of detailed morphological descriptions of this region. On the basis of our recent anatomical examination of this region and a tightly controlled functional magnetic resonance imaging paradigm, the present investigation demonstrated reading-related activity in the region of the angular gyrus that lies between the central and posterior branches of the caudal superior temporal sulcus, namely cytoarchitectonic area PG. Analysis of functional connectivity showed increased functional coupling during reading of area PG with the language areas of Broca and Wernicke, and a region previously identified as the visual word form area. Thus, the parietal reading area has been precisely localized, and its interactions with other cortical areas during reading have been demonstrated.

Experimental induction of reading difficulties in normal readers provides novel insights into the neurofunctional mechanisms of visual word recognition

Phonological and visual dysfunctions may result in reading deficits like those encountered in developmental dyslexia. Here, we use a novel approach to induce similar reading difficulties in normal readers in an event-related fMRI study, thus systematically investigating which brain regions relate to different pathways relating to orthographic-phonological (e.g. grapheme-to-phoneme conversion, GPC) vs. visual processing. Based upon a previous behavioural study (Tholen et al. 2011), the retrieval of phonemes from graphemes was manipulated by lowering the identifiability of letters in familiar vs. unfamiliar shapes. Visual word and letter processing was impeded by presenting the letters of a word in a moving, non-stationary manner. FMRI revealed that the visual condition activated cytoarchitectonically defined area hOC5 in the magnocellular pathway and area 7A in the right mesial parietal cortex. In contrast, the grapheme manipulation revealed different effects localised predominantly in bilateral inferior frontal gyrus (left cytoarchitectonic area 44; right area 45) and inferior parietal lobule (including areas PF/PFm), regions that have been demonstrated to show abnormal activation in dyslexic as compared to normal readers. This pattern of activation bears close resemblance to recent findings in dyslexic samples both behaviourally and with respect to the neurofunctional activation patterns. The novel paradigm may thus prove useful in future studies to understand reading problems related to distinct pathways, potentially providing a link also to the understanding of real reading impairments in dyslexia.

Dissociations between spatial-attentional processes within parietal cortex: insights from hybrid spatial cueing and change detection paradigms

Spatial cueing has been used by many different groups under multiple forms to study spatial attention processes. We will present evidence obtained in brain-damaged patients and healthy volunteers using a variant of this paradigm, the hybrid spatial cueing paradigm, which, besides single-target trials with valid and invalid cues, also contains trials where a target is accompanied by a contralateral competing stimulus (competition trials). This allows one to study invalidity-related processes and selection between competing stimuli within the same paradigm. In brain-damaged patients, lesions confined to the intraparietal sulcus result in contralesional attentional deficits, both during competition and invalid trials, according to a pattern that does not differ from that observed following inferior parietal lesions. In healthy volunteers, however, selection between competing stimuli and invalidity-related processes are partially dissociable, the former relying mainly on cytoarchitectonic areas hIP1-3 in the intraparietal sulcus, the latter on cytoarchitectonic area PF in the right inferior parietal lobule. The activity profile in more posterior inferior parietal areas PFm and PGa, does not distinguish between both types of trials. The functional account for right PF and adjacent areas is further constrained by the activity profile observed during other experimental paradigms. In a change detection task with variable target and distracter set size, for example, these inferior parietal areas show highest activity when the stimulus array consists of only one single target, while the intraparietal sulcus show increased activity as the array contains more targets and distracters. Together, these findings lead us to the hypothesis that right PF functions as a target singleton detector, which is activated when a target stands out from the background, referring both to the temporal background (expectancy) and the momentaneous background (stimulus-driven saliency).

A Comparison Between Volumetric Data Generated by Voxel-Based Morphometry and Manual Parcellation of Multimodal Regions of the Frontal Lobe

Volumetric measurements on structural MR images are an established method to investigate pathology-related volume changes in cortex. Manual volumetric methods have sometimes been referred to as the reference standard for quality control of automatic volumetric methods. While some automatic methods, like VBM, may rely on a template, manual methods use sulci as indirect landmarks for the subdivision of cortex. The purpose of this study was to compare volumetric data generated by MM and VBM on 4 multimodal regions in the frontal lobe. We investigated 4 multimodal frontocortical regions by MM and VBM in patients with frontotemporal lobar degeneration and Alzheimer disease and controls. MM and VBM results were highly correlated for dorsolateral prefrontal cortex, orbitofrontal cortex, and hippocampus, but not for the dorsal and rostral anterior cingulate. VBM results were more consistent with results from previous studies on cingulate in frontotemporal lobar degeneration. Our results may potentially be explained by 2 factors. First, the volume of small cortical regions may be more affected by anatomic variability than large regions in the MM. Second, it has been shown that the location of multimodal cytoarchitectonic areas, such as the cingulate cortex, may be difficult to predict by the appearance of sulci and gyri. While both VBM and the MM may do equally poorly in predicting cytoarchitecture, the MM may add additional unrelated variance caused by anatomic variability. Thus, paradoxically, the higher anatomic precision of the MM may potentially cause a weaker relation to cytoarchitecture.

Poster #56 CLASSIFICATION OF SCHIZOPHRENIA PATIENTS AND HEALTHY CONTROLS FROM STRUCTURAL MRI SCANS VERIFIED IN TWO LARGE INDEPENDENT SAMPLES

The frontal cortex is a heterogeneous region of the cerebral hemisphere consisting of many different cytoarchitectonic areas. The ventrolateral frontal region in the language-dominant hemisphere has been shown to be directly involved in certain aspects of language production. This frontal region includes three motor areas on the precentral gyrus (areas 4, 6VC, and 6VR) that are succeeded anteriorly by area 44 on the pars opercularis and area 45 on the pars triangularis of the inferior frontal gyrus. Areas 44 and 45 are traditionally considered to constitute Broca’s region: the anterior language production cortical zone. The posterior part of the dorsomedial frontal region, including the supplementary motor area, contributes to verbal fluency. Although damage to the various dorsolateral prefrontal cortical areas does not impair language comprehension or production, they do participate in verbal processing by virtue of their role in higher control processes that regulate attention and working memory.

Cytoarchitectonic mapping of the human dorsal extrastriate cortex.

The dorsal visual stream consists of several functionally specialized areas, but most of their cytoarchitectonic correlates have not yet been identified in the human brain. The cortex adjacent to Brodmann area 18/V2 was therefore analyzed in serial sections of ten human post-mortem brains using morphometrical and multivariate statistical analyses for the definition of areal borders. Two previously unknown cytoarchitectonic areas (hOc3d, hOc4d) were detected. They occupy the medial and, to a smaller extent, lateral surface of the occipital lobe. The larger area, hOc3d, is located dorso-lateral to area V2 in the region of superior and transverse occipital, as well as parieto-occipital sulci. Area hOc4d was identified rostral to hOc3d; it differed from the latter by larger pyramidal cells in lower layer III, thinner layers V and VI, and a sharp cortex-white-matter borderline. The delineated areas were superimposed in the anatomical MNI space, and probabilistic maps were calculated. They show a relatively high intersubject variability in volume and position. Based on their location and neighborhood relationship, areas hOc3d and hOc4d are putative anatomical substrates of functionally defined areas V3d and V3a, a hypothesis that can now be tested by comparing probabilistic cytoarchitectonic maps and activation studies of the living human brain.

Meta-analytical definition and functional connectivity of the human vestibular cortex

Contrary to most other sensory systems, no consensus has been reached within the scientific community about the exact locations and functions of human cortical areas processing vestibular information. Metaanalytical modelling using activation likelihood estimation (ALE) for the integration of neuroimaging results has already been successfully applied to several distinct tasks, thereby revealing the cortical localization of cognitive functions. We used the same algorithm and technique with all available and suitable PET and fMRI studies employing a vestibular stimulus. Most consistently across 28 experiments vestibular stimuli evoked activity in the right hemispheric parietal opercular area OP 2 implicating it as the core region for vestibular processing. Furthermore, we took our primary results as a seeding point and fed them into a functional connectivity analysis based on resting-state oscillations in 100 healthy subjects. This subsequent calculation confirmed direct connections of the area OP 2 with every other region found in the meta-analysis, in particular temporo-parietal regions, premotor cortex, and the midcingulate gyrus. Thus revealing a joint vestibular network in accordance with a concept from animal literature termed the inner vestibular circle. Moreover, there was also a significant vestibular connectivity overlap with frontal but not parietal cortical centres responsible for the generation of saccadic eye movements, likely to be involved in nystagmus fast phase generation. This was shown in an additional ocular motor meta-analysis. We conclude that the cytoarchitectonic area OP 2 in the parietal operculum, embedded in a joint vestibular network, should be the primary candidate for the human vestibular cortex. This area may represent the human homologue to the vestibular area PIVC as proposed by Guldin and Grüsser in non-human primates.

Phase sensitivities, excitatory summation fields, and silent suppressive receptive fields of single neurons in the parastriate cortex of the cat

We have recorded single-neuron activity from cytoarchitectonic area 18 of anesthetized (0.4-0.7% isoflurane in 65% N₂O-35% O₂ gaseous mixture) domestic cats. Neurons were identified as simple or complex on the basis of the ratios between the phase-variant (F1) component and the mean firing rate (F0) of spike responses to optimized (orientation, direction, spatial and temporal frequencies, size) high-contrast, luminance-modulated, sine-wave drifting gratings (simple: F1/F0 spike-response ratios > 1; complex: F1/F0 spike-response ratios < 1). The predominance (~80%) of simple cells among the neurons recorded from the principal thalamorecipient layers supports the idea that most simple cells in area 18 might constitute a putative early stage in the visual information processing. Apart from the "spike-generating" regions (the classical receptive fields, CRFs), the receptive fields of three-quarters of area 18 neurons contain silent, extraclassical suppressive regions (ECRFs). The spatial extent of summation areas of excitatory responses was negatively correlated with the strength of the ECRF-induced suppression of spike responses. Lowering the stimulus contrast resulted in an expansion of the summation areas of excitatory responses accompanied by a reduction in the strength of the ECRF-induced suppression. The spatial and temporal frequency and orientation tunings of the ECRFs were much broader than those of the CRFs. Hence, the ECRFs of area 18 neurons appear to be largely "inherited" from their dorsal thalamic inputs. In most area 18 cells, costimulation of CRFs and ECRFs resulted in significant increases in F1/F0 spike-response ratios, and thus there was a contextually modulated functional continuum between the simple and complex cells.

Probabilistic fibre tract analysis of cytoarchitectonically defined human inferior parietal lobule areas reveals similarities to macaques.

The human inferior parietal lobule (IPL) is a multimodal brain region, subdivided in several cytoarchitectonic areas which are involved in neural networks related to spatial attention, language, and higher motor processing. Tracer studies in macaques revealed differential connectivity patterns of IPL areas as the respective structural basis. Evidence for comparable differential fibre tracts of human IPL is lacking. Here, anatomical connectivity of five cytoarchitectonic human IPL areas to 64 cortical targets was investigated using probabilistic tractography. Connection likelihood was assessed by evaluating the number of traces between seed and target against the distribution of traces from that seed to voxels in the same distance as the target. The main fibre tract pattern shifted gradually from rostral to caudal IPL: Rostral areas were predominantly connected to somatosensory and superior parietal areas while caudal areas more strongly connected with auditory, anterior temporal and higher visual cortices. All IPL areas were strongly connected with inferior frontal, insular and posterior temporal areas. These results showed striking similarities with connectivity patterns in macaques, providing further evidence for possible homologies between these two species. This shift in fibre tract pattern supports a differential functional involvement of rostral (higher motor functions) and caudal IPL (spatial attention), with probable overlapping language involvement. The differential functional involvement of IPL areas was further supported by hemispheric asymmetries of connection patterns which showed left-right differences especially with regard to connections to sensorimotor, inferior frontal and temporal areas.

Eye muscle proprioception is represented bilaterally in the sensorimotor cortex

The cortical representation of eye position is still uncertain. In the monkey a proprioceptive representation of the extraocular muscles (EOM) of an eye were recently found within the contralateral central sulcus. In humans, we have previously shown a change in the perceived position of the right eye after a virtual lesion with rTMS over the left somatosensory area. However, it is possible that the proprioceptive representation of the EOM extends to other brain sites, which were not examined in these previous studies. The aim of this fMRI study was to sample the whole brain to identify the proprioceptive representation for the left and the right eye separately. Data were acquired while passive eye movement was used to stimulate EOM proprioceptors in the absence of a motor command. We also controlled for the tactile stimulation of the eyelid by removing from the analysis voxels activated by eyelid touch alone. For either eye, the brain area commonly activated by passive and active eye movement was located bilaterally in the somatosensory area extending into the motor and premotor cytoarchitectonic areas. We suggest this is where EOM proprioception is processed. The bilateral representation for either eye contrasts with the contralateral representation of hand proprioception. We suggest that the proprioceptive representation of the two eyes next to each other in either somatosensory cortex and extending into the premotor cortex reflects the integrative nature of the eye position sense, which combines proprioceptive information across the two eyes with the efference copy of the oculomotor command.

Cyto-, myelo- and chemoarchitecture of the prefrontal cortex of the Cebus monkey

BackgroundAccording to several lines of evidence, the great expansion observed in the primate prefrontal cortex (PfC) was accompanied by the emergence of new cortical areas during phylogenetic development. As a consequence, the structural heterogeneity noted in this region of the primate frontal lobe has been associated with diverse behavioral and cognitive functions described in human and non-human primates. A substantial part of this evidence was obtained using Old World monkeys as experimental model; while the PfC of New World monkeys has been poorly studied.In this study, the architecture of the PfC in five capuchin monkeys (Cebus apella) was analyzed based on four different architectonic tools, Nissl and myelin staining, histochemistry using the lectin Wisteria floribunda agglutinin and immunohistochemistry using SMI-32 antibody.ResultsTwenty-two architectonic areas in the Cebus PfC were distinguished: areas 8v, 8d, 9d, 12l, 45, 46v, 46d, 46vr and 46dr in the lateral PfC; areas 11l, 11m, 12o, 13l, 13m, 13i, 14r and 14c in the orbitofrontal cortex, with areas 14r and 14c occupying the ventromedial corner; areas 32r, 32c, 25 and 9m in the medial PfC, and area 10 in the frontal pole. This number is significantly higher than the four cytoarchitectonic areas previously recognized in the same species. However, the number and distribution of these areas in Cebus were to a large extent similar to those described in Old World monkeys PfC in more recent studies.ConclusionsThe present parcellation of the Cebus PfC considerably modifies the scheme initially proposed for this species but is in line with previous studies on Old World monkeys. Thus, it was observed that the remarkable anatomical similarity between the brains of genera Macaca and Cebus may extend to architectonic aspects. Since monkeys of both genera evolved independently over a long period of time facing different environmental pressures, the similarities in the architectonic maps of PfC in both genera are issues of interest. However, additional data about the connectivity and function of the Cebus PfC are necessary to evaluate the possibility of potential homologies or parallelisms.

Spinogenesis and Pruning in the Anterior Ventral Inferotemporal Cortex of the Macaque Monkey: An Intracellular Injection Study of Layer III Pyramidal Cells

Pyramidal cells grow and mature at different rates among different cortical areas in the macaque monkey. In particular, differences across the areas have been reported in both the timing and magnitude of growth, branching, spinogenesis, and pruning in the basal dendritic trees of cells in layer III. Presently available data suggest that these different growth profiles reflect the type of functions performed by these cells in the adult brain. However, to date, studies have focused on only a relatively few cortical areas. In the present investigation we quantified the growth of the dendritic trees of layer III pyramidal cells in the anterior ventral portion of cytoarchitectonic area TE (TEav) to better comprehend developmental trends in the cerebral cortex. We quantified the growth and branching of the dendrities, and spinogenesis and pruning of spines, from post-natal day 2 (PND2) to four and a half years of age. We found that the dendritic trees increase in size from PND2 to 7 months of age and thereafter became smaller. The dendritic trees became increasingly more branched from PND2 into adulthood. There was a two-fold increase in the number of spines in the basal dendritic trees of pyramidal cells from PND2 to 3.5 months of age and then a 10% net decrease in spine number into adulthood. Thus, the growth profile of layer III pyramidal cells in the anterior ventral portion of the inferotemporal cortex differs to that in other cortical areas associated with visual processing.

Where in-vivo imaging meets cytoarchitectonics: The relationship between cortical thickness and neuronal density measured with high-resolution [18F]flumazenil-PET

MRI-based measurements of surface cortical thickness (SCT) have become a sensitive tool to quantify changes in cortical morphology. When comparing SCT to histological cortical thickness maps, a good correspondence can be found for many but not all human brain areas. Discrepancies especially arise in the sensory motor cortex, where histological cortical thickness is high, but SCT is very low.The aim of this study was to determine whether the relationship between cortical thickness and neuronal density is the same for different cytoarchitectonic areas throughout homo- and heterotypical isocortex. We assessed this relationship using high-resolution [18F]-labelled flumazenil (FMZ) PET and SCT-mapping. FMZ binds to the benzodiazepine GABAA receptor complex which is localized on axo-dendritic synapses, with a cortical distribution closely following the local density of neurons. SCT and voxelwise FMZ binding potential (BPND) were assessed in ten healthy subjects. After partial volume correction, two subsets with a differential relationship between SCT and BPND were identified: a fronto-parietal homotypical subset where neuronal density is relatively constant and mainly independent of SCT, and a subset comprising heterotypical and mainly temporal and occipital homotypical regions where neuronal density is negatively correlated with SCT. This is the first in-vivo study demonstrating a differential relationship between SCT, neuronal density and cytoarchitectonics in humans. These findings are of direct relevance for the correct interpretation of SCT-based morphometry studies, in that there is no simple relationship between apparent cortical thickness and neuronal density, here attributed to FMZ binding, holding for all cortical regions.