Functional role of area 8A in the posterior dorsolateral frontal region of the human brain: A single case study.

Area 8A has traditionally been considered to be the frontal eye field (FEF), i.e. the area for the motor production of eye movements. However, recent research has shown that the FEF lies posteriorly in premotor area 6. Research in macaque monkeys has demonstrated that, in contrast to premotor area 6, which is involved in the production of motor actions, area 8A is implicated in the cognitive allocation of attention to stimuli based on instruction cues. The aim of the present study was to elucidate the specific cognitive role of area 8A by examining a unique patient with a lesion restricted to area 8A, i.e. sparing the premotor cortex. This right-handed male patient underwent neuropsychological assessment and testing on two conditional associative-learning tasks: the motor hand conditional associative-learning task (MCALT) assessing the selection of motor actions based on instruction cues and the visual conditional associative-learning task (VCALT) assessing the selection of visual stimuli based on instruction cues. The patient's performance on the VCALT was significantly impaired compared to control subjects, but performance on the MCALT and on an Eye Movement Control Task was preserved. The present study provides evidence that area 8A is critical for the cognitive process regulating the allocation of attention to different stimuli in the environment, but not in the production of eye movements. These findings enhance understanding of the functional organization of the posterior dorsolateral frontal region in the human brain and suggest a specialized role of area 8A in high-level cognitive processes.

Interaction of the dorsolateral prefrontal cortex with the precuneal medial parietal cortex for the monitoring of information in working memory in the macaque monkey.

The executive control process of monitoring information in working memory depends on the mid-dorsolateral prefrontal cortical region (cytoarchitectonic areas 46 and 9/46) in interaction with the hippocampal memory system. Anatomical studies demonstrated strong connectivity between the mid-dorsolateral prefrontal cortex and the medial parietal area PGm that lies on the precuneus. Area PGm is also strongly connected with the attentional system on the lateral inferior parietal lobule (area PG) and the limbic retrosplenial/posterior cingulate region that interacts with the hippocampal memory system. Thus, in terms of anatomical connectivity, area PGm appears to be a critical node for the integration of executive control processing from the prefrontal cortex with the online attentional and memory related processing. This hypothesis was tested in macaque monkeys with the crossed unilateral lesion methodology. A unilateral lesion in the mid-dorsolateral prefrontal cortex was combined with a unilateral lesion in area PGm in the opposite hemisphere. The results demonstrated an impairment on the externally ordered working memory task that assesses the monitoring of information in working memory. Thus, the medial parietal area PGm is a critical node in mediating the functional interaction between the prefrontal region for the executive control process of monitoring information and the memory system.

Morphological patterns and spatial probability maps of the inferior frontal sulcus in the human brain.

The inferior frontal sulcus (ifs) is a prominent sulcus on the lateral frontal cortex, separating the middle frontal gyrus from the inferior frontal gyrus. The morphology of the ifs can be difficult to distinguish from adjacent sulci, which are often misidentified as continuations of the ifs. The morphological variability of the ifs and its relationship to surrounding sulci were examined in 40 healthy human subjects (i.e., 80 hemispheres). The sulci were identified and labeled on the native cortical surface meshes of individual subjects, permitting proper intra-sulcal assessment. Two main morphological patterns of the ifs were identified across hemispheres: in Type I, the ifs was a single continuous sulcus, and in Type II, the ifs was discontinuous and appeared in two segments. The morphology of the ifs could be further subdivided into nine subtypes based on the presence of anterior and posterior sulcal extensions. The ifs was often observed to connect, either superficially or completely, with surrounding sulci, and seldom appeared as an independent sulcus. The spatial variability of the ifs and its various morphological configurations were quantified in the form of surface spatial probability maps which are made publicly available in the standard fsaverage space. These maps demonstrated that the ifs generally occupied a consistent position across hemispheres and across individuals. The normalized mean sulcal depths associated with the main morphological types were also computed. The present study provides the first detailed description of the ifs as a sulcal complex composed of segments and extensions that can be clearly differentiated from adjacent sulci. These descriptions, together with the spatial probability maps, are critical for the accurate identification of the ifs in anatomical and functional neuroimaging studies investigating the structural characteristics and functional organization of this region in the human brain.

The superior frontal sulcus in the human brain: Morphology and probability maps.

The superior frontal sulcus (SFS) is the major sulcus on the dorsolateral frontal cortex that defines the lateral limit of the superior frontal gyrus. Caudally, it originates near the superior precentral sulcus (SPRS) and, rostrally, it terminates near the frontal pole. The advent of structural neuroimaging has demonstrated significant variability in this sulcus that is not captured by the classic sulcal maps. The present investigation examined the morphological variability of the SFS in 50 individual magnetic resonance imaging (MRI) scans of the human brain that were registered to the Montreal Neurological Institute (MNI) standard stereotaxic space. Two primary morphological patterns were identified: (i) the SFS was classified as a continuous sulcus or (ii) the SFS was a complex of sulcal segments. The SFS showed a high probability of merging with neighbouring sulci on the superior and middle frontal gyri and these patterns were documented. In addition, the morphological variability and spatial extent of the SFS were quantified using volumetric and surface spatial probability maps. The results from the current investigation provide an anatomical framework for understanding the morphology of the SFS, which is critical for the interpretation of structural and functional neuroimaging data in the dorsolateral frontal region, as well as for improving the accuracy of neurosurgical interventions.

On the evolution of polysensory superior temporal sulcus and middle temporal gyrus: A key component of the semantic system in the human brain.

The primary auditory cortex and other early auditory cortical areas lie on Heschl's gyrus within the Sylvian fissure. On the adjacent lateral surface of the superior temporal gyrus, the cortex processes higher order auditory information leading to auditory perception. On the ventral surface of the temporal lobe in the primate brain, there are areas that process higher order visual information leading to visual perception. These sensory-specific auditory and visual processing regions are separated by areas that integrate multisensory information within the deep superior temporal sulcus in both the macaque monkey and human brains. In the human brain, the multisensory integration cortex expands and forms the adjacent middle temporal gyrus. The expansion of this multisensory region in the language-dominant hemisphere of the human brain is critical for the emergence of semantic processing, namely, the processing of conceptual information that is not sensory specific but rather relies on multisensory integration.

Exploring public knowledge and perceptions regarding per os OTC pain-relieving medications: the case of paracetamol (acetaminophen).

BACKGROUND: Over-the-counter medications (OTC) are safe and effective when patients follow the patient's information leaflet (PIL) instructions and/or the instructions given by healthcare professionals (HCPs). However, OTC medications could be harmful and unsafe when individuals do not follow the given instructions and/or when their understanding about the proper use of OTC medications is incorrect. This study aimed to investigate the knowledge and perceptions of people regarding paracetamol use in the Republic of Cyprus. METHODS: This cross-sectional study, which belongs to quantitative research methods, included participants visiting community pharmacies in the following three cities of the Republic of Cyprus: Nicosia, Limassol and Larnaca. Participation in the study was voluntary and anonymous. Participants responded to the survey-based questionnaire, which concerned their knowledge and views on paracetamol use. After the data collection, responses were tabulated and analysed statistically. RESULTS: The original compound was shown to be more well-known compared to generics. A notable percentage of respondents-ranging between 13.0% (N = 49) and 29.8% (N = 112)-answered incorrectly that broadly used non-steroidal anti-inflammatory drugs (NSAIDs) contain paracetamol. Furthermore, a remarkable percentage of respondents (71.5%, N = 269 and 50.3%, N = 189, respectively) falsely believed that two widely used combination products in the market of Cyprus (Paracetamol and Hyoscine-N-butylbromide; Paracetamol and Codeine and Caffeine) did not contain paracetamol. A notable percentage of participants (27.6%, N = 100) believed that paracetamol causes low toxicity. More than a third of the respondents (40.2%, N = 149) drink alcohol together with or slightly after consuming paracetamol products. This viewpoint was linked with the participants' attitude towards consuming paracetamol medications after drinking alcohol (OR for consuming alcohol versus not consuming alcohol 0.100, 95% CI 0.044-0.225, p = 0.000). CONCLUSIONS: To the best of our knowledge, this is the first study conducted in the Republic of Cyprus on this topic. Paracetamol is frequently consumed by individuals, both in its generic and original forms. However, the study showed that respondents often misperceive NSAIDs and paracetamol-containing medications. In addition, it is identified that there is a lack of education among people about the safe and effective use of paracetamol, namely, indications, potential side effects, maximum daily dose, alcohol consumption, and the potential risks of hepatotoxicity. The study contributed to the current published literature as it showed that there is a significant public health issue, for which appropriate measures can be established by the respective Authorities of Cyprus.

The relevance of the unique anatomy of the human prefrontal operculum to the emergence of speech.

Identifying the evolutionary origins of human speech remains a topic of intense scientific interest. Here we describe a unique feature of adult human neuroanatomy compared to chimpanzees and other primates that may provide an explanation of changes that occurred to enable the capacity for speech. That feature is the Prefrontal extent of the Frontal Operculum (PFOp) region, which is located in the ventrolateral prefrontal cortex, adjacent and ventromedial to the classical Broca's area. We also show that, in chimpanzees, individuals with the most human-like PFOp, particularly in the left hemisphere, have greater oro-facial and vocal motor control abilities. This critical discovery, when combined with recent paleontological evidence, suggests that the PFOp is a recently evolved feature of human cortical structure (perhaps limited to the genus Homo) that emerged in response to increasing selection for cognitive and motor functions evident in modern speech abilities.

The importance of the dorsal branch of the arcuate fasciculus in phonological working memory.

Phonological working memory (PWM) is important for language learning and processing. The most studied language brain regions are the classical Broca's area on the inferior frontal gyrus and Wernicke's area on the posterior temporal region and their anatomical connection via the classic arcuate fasciculus (AF) referred to here as the ventral AF (AFv). However, areas on the middle frontal gyrus (MFG) are essential for PWM processes. There is also a dorsal branch of the AF (AFd) that specifically links the posterior temporal region with the MFG. Furthermore, there is the temporo-frontal extreme capsule fasciculus (TFexcF) that courses ventrally and links intermediate temporal areas with the lateral prefrontal cortex. The AFv, AFd and TFexcF were dissected virtually in the same participants who performed a PWM task in a functional magnetic resonance imaging study. The results showed that good performance on the PWM task was exclusively related to the properties of the left AFd, which specifically links area 8A (known to be involved in attentional aspects of executive control) with the posterior temporal region. The TFexcF, consistent with its known anatomical connection, was related to brain activation in area 9/46v of the MFG that is critical for monitoring the information in memory.

A revised perspective on the evolution of the lateral frontal cortex in primates.

Detailed neuroscientific data from macaque monkeys have been essential in advancing understanding of human frontal cortex function, particularly for regions of frontal cortex without homologs in other model species. However, precise transfer of this knowledge for direct use in human applications requires an understanding of monkey to hominid homologies, particularly whether and how sulci and cytoarchitectonic regions in the frontal cortex of macaques relate to those in hominids. We combine sulcal pattern analysis with resting-state functional magnetic resonance imaging and cytoarchitectonic analysis to show that old-world monkey brains have the same principles of organization as hominid brains, with the notable exception of sulci in the frontopolar cortex. This essential comparative framework provides insights into primate brain evolution and a key tool to drive translation from invasive research in monkeys to human applications.

Neural cognitive signals during spontaneous movements in the macaque.

The single-neuron basis of cognitive processing in primates has mostly been studied in laboratory settings where movements are severely restricted. It is unclear, therefore, how natural movements might affect neural signatures of cognition in the brain. Moreover, studies in mice indicate that body movements, when measured, account for most of the neural dynamics in the cortex. To examine these issues, we recorded from single-neuron ensembles in the prefrontal cortex in moving monkeys performing a cognitive task and characterized eye, head and body movements using video tracking. Despite considerable trial-to-trial movement variability, single-neuron tuning could be precisely measured and decision signals accurately decoded on a single-trial basis. Creating or abolishing spontaneous movements through head restraint and task manipulations had no measurable impact on neural responses. However, encoding models showed that uninstructed movements explained as much neural variance as task variables, with most movements aligned to task events. These results demonstrate that cognitive signals in the cortex are robust to natural movements, but also that unmeasured movements are potential confounds in cognitive neurophysiology experiments.

Optimal blocking of the cerebral cortex for cytoarchitectonic examination: a neuronavigation-based approach.

Certain sulci of the human cerebral cortex hold consistent relationships to cytoarchitectonic areas (e.g. the primary motor cortical area 4 and the somatosensory cortical area 3 occupy the anterior and posterior banks of the central sulcus, respectively). Recent research has improved knowledge of the cortical sulci and their variability across individuals. However, other than the so-called primary sulci, understanding of the precise relationships cortical folds hold with many cytoarchitectonic areas remains elusive. To examine these relationships, the cortex must be blocked, sectioned, and histologically processed in a manner that allows the cytoarchitectonic layers to be clearly observed. The optimal strategy to view the cytoarchitecture is to block and section the cortex perpendicular to the sulcal orientation. Most cytoarchitectonic investigations of the cortex, however, have been conducted on specimens cut along a single axis (e.g. the coronal plane), which distorts the appearance of the cytoarchitectonic layers within parts of the cortical ribbon not sectioned optimally. Thus, to understand further the relationships between sulci and cytoarchitectonic areas, the cortex should be sectioned optimally to the sulci of interest. A novel approach for blocking the cortex optimally using structural magnetic resonance imaging (MRI) and surgical neuronavigation tools is presented here.

Morphological patterns and spatial probability maps of the superior parietal sulcus in the human brain.

The superior parietal sulcus (SPS) is the defining sulcus within the superior parietal lobule (SPL). The morphological variability of the SPS was examined in individual magnetic resonance imaging (MRI) scans of the human brain that were registered to the Montreal Neurological Institute (MNI) standard stereotaxic space. Two primary morphological patterns were consistently identified across hemispheres: (i) the SPS was identified as a single sulcus, separating the anterior from the posterior part of the SPL and (ii) the SPS was found as a complex of multiple sulcal segments. These morphological patterns were subdivided based on whether the SPS or SPS complex remained distinct or merged with surrounding parietal sulci. The morphological variability and spatial extent of the SPS were quantified using volumetric and surface spatial probabilistic mapping. The current investigation established consistent morphological patterns in a common anatomical space, the MNI stereotaxic space, to facilitate structural and functional analyses within the SPL.

Interhemispheric functional brain connectivity predicts new language learning success in adults.

Investigating interhemispheric interactions between homologous cortical regions during language processing is of interest. Despite prevalent left hemisphere lateralization of language, the right hemisphere also plays an important role and interhemispheric connectivity is influenced by language experience and is implicated in second language (L2) acquisition. Regions involved in language processing have differential connectivity to other cortical regions and to each other, and play specific roles in language. We examined the interhemispheric interactions of subregions of the inferior frontal gyrus (areas 44 and 45), the adjacent area 9/46v in the middle frontal gyrus, the superior temporal gyrus (STG), and the posterior inferior parietal lobule (pIPL) in relation to distinct and specific aspects of L2 learning success. The results indicated that the connectivity between left and right areas 44 and 9/46v predicted improvement in sentence repetition, connectivity between left and right area 45 and mid-STG predicted improvement in auditory comprehension, and connectivity between left and right pIPL predicted improvement in reading speed. We show interhemispheric interactions in the specific context of facilitating performance in adult L2 acquisition that follow an anterior to posterior gradient in the brain, and are consistent with the respective roles of these regions in language processing.

Specific disruption of the ventral anterior temporo-frontal network reveals key implications for language comprehension and cognition.

Recent investigations have raised the question of the role of the anterior lateral temporal cortex in language processing (ventral language network). Here we present the language and overall cognitive performance of a rare male patient with chronic middle cerebral artery cerebrovascular accident with a well-documented lesion restricted to the anterior temporal cortex and its connections via the extreme capsule with the pars triangularis of the inferior frontal gyrus (i.e. Broca's region). The performance of this unique patient is compared with that of two chronic middle cerebral artery cerebrovascular accident male patients with damage to the classic dorsal posterior temporo-parietal language system. Diffusion tensor imaging is used to reconstruct the relevant white matter tracts of the three patients, which are also compared with those of 10 healthy individuals. The patient with the anterior temporo-frontal lesion presents with flawless and fluent speech, but selective impairment in accessing lexico-semantic information, in sharp contrast to the impairments in speech, sentence comprehension and repetition observed after lesions to the classic dorsal language system. The present results underline the contribution of the ventral language stream in lexico-semantic processing and higher cognitive functions, such as active selective controlled retrieval.

Splenial Callosal Disconnection in Right Hemianopic Patients Induces Right Visual-Spatial Neglect.

Posterior cerebral artery (PCA) territory infarction involving occipital cortical damage can give rise to contralateral homonymous hemianopia. Here, we report two rare cases of patients with lesions in the left hemisphere PCA territory who developed right visuo-spatial neglect. One patient suffered right hemianopia and right visuo-spatial neglect after a stroke that damaged the left primary visual cortex and the callosal splenial fibers. The other unique case is of a patient who had a brain tumor in the posterior cerebral region in the left hemisphere and initially exhibited only right hemianopia that developed into right visuo-spatial neglect after tumor resection that included the splenial fibers. These cases indicate that, as in cases with damage in the right PCA territory, lesions in the left PCA yield visuo-spatial neglect when the damage produces contralateral hemianopia and concomitant disconnection of the splenium of the corpus callosum, which interferes with the arrival of visual inputs from the intact right to the lesioned left hemisphere. These results also emphasize the necessity of sparing the splenial fibers in surgical interventions in patients who exhibit hemianopia.

Sulci and gyri are topological cerebral landmarks in individual subjects: a study of brain navigation during tumour resection.

Surgical resection of brain tumours aims at the maximal safe resection of the pathological tissue with minimal functional impairment. To achieve this objective, reliable anatomical landmarks are indispensable to navigate into the brain. The neuronavigation system can provide information to target the location of the patient's lesion, but after the craniotomy, a brain shift and relaxation mismatch with it often occur. By contrast, sulci/gyri are topological cerebral landmarks in individual patients and do shift with the brain parenchyma during lesion removal, but remain independent from brain shift in relation to the sulci/gyri. Here, we present a case report of a novel strategy based on anatomical landmarks to guide intraoperative brain tumour resection, without using a standard neuronavigation system. A preoperative brain mapping of the peri-tumoural sulci by the MRI and surface reconstruction was followed by confirmation of the anatomical landmarks for the motor cortex using navigated transcranial magnetic stimulation. The resulting location was used as a seed for diffusion tensor imaging tractography to reconstruct the corticospinal tracts. These selected cortical landmarks (sulci/gyri) delimited the margins of the two lesions and the specific location under which the corticospinal tract courses, thus facilitating monitoring of the peri-tumoural region during brain resection. In this case, 96% of the brain tumour from the pericentral somatomotor region was successfully removed without chronic post-operative motor impairments. This approach is based on cortical anatomy that is fixed during surgery and does not suffer from the brain shift that could misplace the lesion according to the neuronavigation system.

Spatial probability maps of the segments of the postcentral sulcus in the human brain.

The postcentral sulcus is the posterior boundary of the postcentral gyrus where the somatosensory cortex is represented. In the human brain, the postcentral sulcus is composed of five distinct segments that are related to the somatosensory representation of different parts of the body. Segment 1 of the postcentral sulcus, located near the dorsomedial boundary of each hemisphere, is associated with toe/leg representations, segment 2 with arm/hand representations, segment 3 with blinking, and segments 4 and 5, which are near the lateral fissure and the parietal operculum, with the mouth and tongue representations. The variability in location and spatial extent of these five segments were quantified in 40 magnetic resonance imaging (MRI) anatomical brain scans registered to the stereotaxic space of the Montreal Neurological Institute (MNI space), in the form of volumetric (using MINC Toolkit) and surface (using FreeSurfer) spatial probability maps. These probability maps can be used by researchers and clinicians to improve the localization of the segments of the postcentral sulcus in MRI images of interest and also to improve the interpretation of the location of activation peaks generated in functional neuroimaging studies investigating somatosensory cortex.

Frontoparietal Anatomical Connectivity Predicts Second Language Learning Success.

There is considerable individual variability in second language (L2) learning abilities in adulthood. The inferior parietal lobule, important in L2 learning success, is anatomically connected to language areas in the frontal lobe via the superior longitudinal fasciculus (SLF). The second and third branches of the SLF (SLF II and III) have not been examined separately in the context of language, yet they are known to have dissociable frontoparietal connections. Studying these pathways and their functional contributions to L2 learning is thus of great interest. Using diffusion MRI tractography, we investigated individuals undergoing language training to explore brain structural predictors of L2 learning success. We dissected SLF II and III using gold-standard anatomical definitions and related prelearning white matter integrity to language improvements corresponding with hypothesized tract functions. SLF II properties predicted improvement in lexical retrieval, while SLF III properties predicted improvement in articulation rate. Finer grained separation of these pathways enables better understanding of their distinct roles in language, which is essential for studying how anatomical connectivity relates to L2 learning abilities.

Broca's area and the search for anatomical asymmetry: commentary and perspectives.

We present a brief commentary on the field's search for an anatomical asymmetry between Broca's area and its homologue in the non-dominant hemisphere, focusing on a selection of studies, including research from the last decade. We demonstrate that, several years after the influential review of Keller and colleagues from 2009, and despite recent advances in neuroimaging, the existence of a structural asymmetry of Broca's area is still controversial. This is especially the case for studies of the macroanatomy of this region. We point out the inconsistencies in methodology across studies that could account for the discrepancy in results. Investigations of the microstructure of Broca's area show a trend of a leftward asymmetry, but it is still unclear how these results relate to language dominance. We suggest that it may be necessary to combine multiple metrics in a systematic manner to find robust asymmetries and to expand the regional scope of structural investigations. Finally, based on the current state of the literature, we should not rule out the possibility that language dominance may simply not be reflected in local anatomical differences in the brain.