Association between the brain-derived neurotrophic factor Val66Met polymorphism and brain morphology in a Japanese sample of schizophrenia and healthy comparisons

Magnetic resonance imaging was used to investigate the relation between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and volumetric measurements for the medial temporal lobe structures (amygdala, hippocampus, and parahippocampal gyrus) and prefrontal sub-regions (the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, ventral medial prefrontal cortex, orbitofrontal cortex, and straight gyrus) in a Japanese sample of 33 schizophrenia patients and 29 healthy subjects. For the controls, the Met carriers had significantly smaller parahippocampal and left superior frontal gyri than the Val homozygotes. The schizophrenia patients carrying the Met allele had a significantly smaller right parahippocampal gyrus than those with the Val/Val genotype, but the genotype did not affect the prefrontal regions in schizophrenia patients. These findings might reflect different genotypic effects of BDNF on brain morphology in schizophrenia patients and healthy controls, implicating the possible role of the brain morphology as an endophenotype for future genetic studies in schizophrenia.     

Differential involvement of regions of rostral prefrontal cortex (Brodmann area 10) in time- and event-based prospective memory.

Rostral prefrontal cortex (approximating Brodmann area 10) has been shown repeatedly to have a role in the maintenance and realization of delayed intentions that are triggered by event cues (i.e., event-based prospective memory). The cerebral organization of the processes associated with the use of time cues (time-based prospective memory) has however received less attention. In two positron emission tomography (PET) studies we therefore examined brain activity associated with time- and event-based prospective memory tasks. In the time-based condition of the first study, young healthy volunteers were asked to make a prospective response based on their self-estimation of the passage of time while engaged in an attention-demanding ongoing activity. In the time-based condition of the second study, participants had a clock available in the ongoing task display and did not need to estimate the time for the prospective response. In the event-based condition of both studies, participants were asked to make a prospective response when prospective cues were presented in ongoing trials. Both studies showed activation differences in rostral prefrontal cortex according to whether the task was time- or event-based. In study one, an area of left superior frontal gyrus was more active in the time-based condition. In study two, three rostral prefrontal regions were more active in the time-based condition: right superior frontal gyrus, anterior medial frontal lobe and anterior cingulate gyrus. A region in left superior frontal gyrus, different from the area found in the first study, was more active in the event-based condition. These results indicate involvement of multiple brain regions of rostral prefrontal cortex in time- and event-based prospective memory. The results are interpreted as reflecting the differing processing demands made by event- or time-based prospective memory tasks, and the differing demands of time-based tasks according to whether a clock is present as an aid.     

Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task

Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia.     

Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?

BACKGROUND: Functional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the potential role of task-related deactivation. METHOD: Thirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: The controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent. CONCLUSIONS: Patients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the 'default mode network' implicated in functions related to maintaining one's sense of self.     

Activation of brain regions using task-state FMRI in patients with mild traumatic brain injury: a meta-analysis

Activation likelihood estimation meta-analysis was performed to examine the activation characteristics of cognition-related brain regions in patients with mild traumatic brain injury (mTBI). The databases PubMed, Ovid, Cochrane Library, Google Scholar, CNKI, WFSD, and VIP were systematically searched. The software Ginger-ALE 3.0.2 was used for coordinate unification and meta-analysis. Seven studies with a total of 314 subjects were included. Meta-analysis results indicated that compared with healthy subjects, mTBI patients had enhanced activation in the left anterior angular gyrus, left occipital joint visual, left midbrain, right temporal angular gyrus, right cerebellar tonsil, left frontal insula, and right inferior frontal gyrus. mTBI patients had attenuated activation in the right dorsolateral prefrontal lobe, left cerebellar anterior lobe, left dorsolateral prefrontal lobe, right middle frontal gyrus, right posterior cingulate gyrus, left joint visual, left supramarginal gyrus, left middle frontal gyrus, right precuneus, left dorsolateral prefrontal cortex, right frontal eye field, right lower parietal gyrus, corpus callosum, right frontal pole region, and left prefrontal lobe. Further joint analysis revealed that the dorsolateral prefrontal lobe of the right middle frontal gyrus was a region of attenuated co-activation. The dorsolateral prefrontal lobe of the right middle frontal gyrus showing attenuated activation was the main brain region distinguishing mTBI patients from healthy subjects. Cognitive deficits could be associated with attenuated activation in the dorsolateral prefrontal lobe of the right middle frontal gyrus, which could be due to a decline in the recruitment ability of the neural network involved in controlling attention.     

Evidence for a dysfunctional retrosplenial cortex in patients with schizophrenia: a functional magnetic resonance imaging study with a semantic-perceptual contrast

We investigated whether the retrosplenial and the posterior cingulate cortex (RS-PCC) is functionally impaired in schizophrenia patients. Therefore, we measured functional magnetic resonance imaging (fMRI) signal changes associated with a synonym-judgment task known to activate, among other areas, the RS-PCC. Compared to 12 matched control subjects, 12 schizophrenia patients exhibited reliably weaker activations in the RS-PCC, the dorsolateral prefrontal cortex and the left orbitofrontal cortex (P < 0.05, corrected). Differences in frontal activations are in line with previous studies showing a structurally and functionally affected prefrontal cortex in schizophrenia. The impaired RS-PCC functionality in a semantic task may relate to verbal memory deficits frequently observed in schizophrenia patients, because this region is pivotal for gating information into the medial temporal lobe memory system.     

An fMRI study of episodic memory: retrieval of object, spatial, and temporal information

Sixteen participants viewed a videotaped tour of 4 houses that highlighted a series of objects and their spatial locations. Participants were tested for memory of object, spatial, and temporal-order information while undergoing functional magnetic resonance imaging. Preferential activation was observed in the right parahippocampal gyrus during the retrieval of spatial-location information. Retrieval of contextual information (spatial location and temporal order) was associated with activation in the right dorsolateral prefrontal cortex. In bilateral posterior parietal regions, greater activation was associated with processing of visual scenes regardless of the memory judgment. These findings support current theories positing roles for frontal and medial temporal regions during episodic retrieval and suggest a specific role for the hippocampal complex in the retrieval of spatial-location information.     

Virtual needle pain stimuli activates cortical representation of emotions in normal volunteers

Psychological factors are known to play an extremely important role in the maintenance and development of chronic pain conditions. However, it is unclear how such factors relate to the central neural processing of nociceptive transmission in healthy individuals. To investigate this issue, the activation of the brain was studied in 30 healthy volunteers responding to virtual pain stimuli by fMRI. In the first series of the study (non-preconditioned study), 15 participants were shown a digital video demonstrating an injection needle puncturing the right palm. In the second series of the study (pre-conditioned study), same-task paradigms were used for another 15 participants. Prior to the fMRI session, real needle punctuate stimuli were applied to the right palm of participants for pre-conditioning. fMRI analysis revealed that bilateral activations in anterior insula (BA45), parietal operculum (S2: BA40), premotor area, medial globus pallidus, inferior occipital gyrus (BA18), left temporal association cortex, right fusiform gyrus, right parietal association cortex and cerebellum occurred due to the task in the preconditioned group. On the other hand, right parietal operculum (S2: BA40), premotor area, parietal association cortex, left inferior frontal gyrus and bilateral temporal association cortex were activated in the non-preconditioned group. In addition, activation of anterior insula, inferior frontal gyrus, precentral gyrus and cerebellum significantly increased in the preconditioned group compared with the non-preconditioned group. These results suggest that the virtual needle puncture task caused memory retrieval of unpleasant experiences which is possibly related to empathy for pain, resulting in the activation of specific brain areas.     

Spatial working memory specific activity in dorsal prefrontal cortex? Disparate answers from fMRI beta-weight and timecourse analysis

Visual spatial processing and object processing rely on dorsal and ventral cortical pathways, respectively. Whether this functional segregation exists in the prefrontal cortex is currently a source of debate. Using functional MRI (fMRI), there has been some evidence that the superior frontal sulcus (within dorsal prefrontal cortex) is specialised for spatial working memory, while ventral prefrontal cortex is associated with object working memory. Employing beta-weight analysis, Postle, Berger, Taich, and D'Esposito (2000) challenged these results, finding no differential activity associated with spatial working memory versus two-dimensional saccades in the superior frontal sulcus. In the present reanalysis of Postle et al.'s data, both beta-weight analysis and event-related timecourse analysis were utilised. Beta-weight analysis results replicated Postle et al.; however, timecourse analysis revealed greater activity associated with spatial working memory versus two-dimensional saccades in the superior frontal sulcus. Thus, identical fMRI data analysed via distinct methods yielded results with different theoretical conclusions.     

Spatial working memory specific activity in dorsal prefrontal cortex? Disparate answers from fMRI beta-weight and timecourse analysis

Visual spatial processing and object processing rely on dorsal and ventral cortical pathways, respectively. Whether this functional segregation exists in the prefrontal cortex is currently a source of debate. Using functional MRI (fMRI), there has been some evidence that the superior frontal sulcus (within dorsal prefrontal cortex) is specialised for spatial working memory, while ventral prefrontal cortex is associated with object working memory. Employing beta-weight analysis, Postle, Berger, Taich, and D'Esposito (2000) challenged these results, finding no differential activity associated with spatial working memory versus two-dimensional saccades in the superior frontal sulcus. In the present reanalysis of Postle et al.'s data, both beta-weight analysis and event-related timecourse analysis were utilised. Beta-weight analysis results replicated Postle et al.; however, timecourse analysis revealed greater activity associated with spatial working memory versus two-dimensional saccades in the superior frontal sulcus. Thus, identical fMRI data analysed via distinct methods yielded results with different theoretical conclusions.     

Event-related fMRI of word classification and successful word recognition in subjects at genetically enhanced risk of schizophrenia

BACKGROUND: Verbal declarative memory is a core deficit in schizophrenia patients, seen to a lesser extent in unaffected biological relatives. Neuroimaging studies suggest volumetric differences and aberrant function in prefrontal and temporal regions in schizophrenia patients compared to controls. These deficits are also reflected in the small number of similar investigations in unaffected biological relatives. However, it is unclear the extent to which dysfunction is genetically mediated or a feature of the established illness. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation in 68 biological relatives of schizophrenia patients (of whom 27 experienced transient or isolated psychotic symptoms) and 21 controls during verbal classification and recognition. RESULTS: During word classification, the high-risk group showed a greater response relative to controls in the right inferior frontal gyrus. During correct recognition (relative to correct rejection), the high-risk group showed significantly greater response relative to controls in the right cerebellum. When the high-risk group was split into those with (HR+) and without (HR-) psychotic symptoms, the increased response in the right inferior frontal gyrus was only seen when the HR+ were compared to controls. The greater cerebellar response was seen when both HR groups were compared to controls. CONCLUSIONS: Activation increases in the right inferior frontal gyrus and cerebellum in high-risk subjects compared to controls during a relatively low-load memory task are likely to represent compensation for genetically mediated abnormalities. This is consistent with a leftward shift of the inverted 'U' load-response model of cognitive function in schizophrenia.     

The role of prefrontal cortex in visuo-spatial planning: a repetitive TMS study

The visuo-spatial planning process is based on an “opportunistic” combination of heuristics and strategies, carried out in small units during the execution of plans. In order to investigate the functional role of the prefrontal cortex in heuristic switching, 42 healthy controls performed a labyrinth crossing task (the Maps Test). During this computerized version of the Travelling Salesperson Problem, subjects had to decide which order of locations optimizes total travel time and distance. This task was performed with and without 1 Hz repetitive transcranial magnetic stimulation (rTMS), which exerts an inhibitory action on the targeted area, applied during the task over bilateral frontal sites (active stimulation) and parieto-occipital site (sham stimulation). Only repetitive bilateral rTMS over F3 and F4 significantly decreased the number of strategies with changes of heuristics, and increased the number of movements required to solve the task. This behaviour contrasts with the performance of healthy subjects in the planning task, but is consistent with the performance of frontal traumatic brain injury patients. The results indicate that, in a visuo-spatial problem-solving task, the prefrontal cortex is involved in the switching between heuristics during the execution of a plan.     

Neural correlates of age-related verbal episodic memory decline: a PET study with combined subtraction/correlation analysis

Using PET, we have determined the neural substrates of age-related verbal episodic memory decline. Twelve young and twelve older healthy volunteers (mean age; 22 and 59 years, respectively) were scanned while performing encoding and retrieval tasks. Retrieval performance was lower in old than in young subjects. The PET data were analyzed using a combined subtraction/correlation approach. Classic subtraction disclosed prefrontal rCBF increases common to both groups, distributed bilaterally during encoding and exclusively right-sided during retrieval, without between-group differences. The correlation analysis between PET activity during encoding and subsequent retrieval performance revealed significant correlations for the left hippocampal region in both groups, but for the right inferior frontal gyrus in the older subjects only. Thus, lower performance in older subjects during an episodic retrieval task may reflect a combination of (i) subtle encoding dysfunction, evidenced by more widespread activity-performance correlations and (ii) less efficient retrieval, as evidenced by unaltered activation pattern (as revealed by the classic subtraction method) despite reduced performance. These exploratory findings suggest the aged brain may be unable to compensate for reduced efficiency of right prefrontal cortex by additional left frontal activation.     

Neonatal lesions of the ventral hippocampus in rats lead to prefrontal cognitive deficits at two maturational stages

This experiment assessed the effect of neonatal ventral hippocampus lesions in rats, a heuristic approach to model schizophrenia, on continuous delayed alternation and conditional discrimination learning performance before and after complete cerebral maturation. Delays (0, 5, 15, and 30 s) were introduced in the tasks to help dissociate between a hippocampal and a prefrontal cortex dysfunction. At postnatal day (PND) 6 or 7, rats received bilateral microinjections of ibotenic acid or phosphate-buffered saline in the ventral hippocampus. From PND 26 to PND 35, rats were tested on the alternation task in a T-maze; from PND 47 to PND 85, the same rats were tested in the discrimination task where a stimulus and a response location had to be paired. Deficits in ventral hippocampus-lesioned rats were observed in both tasks whether a delay was introduced before a response or not. Impaired performance regardless of delay length, combined with high rates of perseverative errors, suggested a post-lesional prefrontal cortex dysfunction which persisted from the juvenile stage into adulthood. Premature cognitive impairments could not be predicted on the basis of the neurodevelopmental animal model of schizophrenia. Nevertheless, they appear consistent with accounts of premorbidly compromised memory, both immediate and delayed, in subgroups of schizophrenia patients.     

Reduced activation to implicit affect induction in euthymic bipolar patients: an fMRI study

OBJECTIVE: To examine whether euthymic bipolar patients engage similar or contrasting brain regions as healthy subjects when responding to implicit affect induction. METHODS: The study examined 10 euthymic patients with bipolar I disorder, and 10 age- and gender-matched healthy subjects using event-related functional magnetic resonance imaging (fMRI) while subjects engaged in a modified word-based memory task designed to implicitly evoke negative, positive or no affective change. The activation paradigm involved nominating whether a target word was contained within a previously presented word list using specified response keys. RESULTS: The fMRI task produced significantly greater activation in healthy subjects as compared to patients in response to both negative and positive affect in the anterior and posterior cingulate, medial prefrontal cortex, middle frontal and right parahippocampal gyri. Only negative affect produced significantly greater activation in the postcentral gyrus, inferior parietal lobule, thalamus and putamen and only positive affect achieved the same in the precentral, superior temporal and lingual gyri, precuneus, cuneus, caudate, pons, midbrain and cerebellum. There were no brain regions in which responses were greater in patients as compared to healthy subjects. There were no statistically significant differences between the groups with respect to speed or accuracy. CONCLUSIONS: Diminished prefrontal, cingulate, limbic and subcortical neural activity in euthymic bipolar patients as compared to healthy subjects is suggestive of emotional compromise that is independent of cognitive and executive functioning. This finding is of clinical importance and has implications both for the diagnosis and treatment of bipolar disorder. Future studies should aim to replicate these findings and examine the development of bipolar disorder, investigating in particular the effects of medication.     

Fronto-striatal hypoactivation during correct information retrieval in patients with schizophrenia: an fMRI study

Working memory (WM) deficits are core symptoms of schizophrenia. Differing behavioral performance is known to represent a potent moderating variable when investigating the neural correlates of working memory in patients with schizophrenia compared with healthy controls. The present functional magnetic resonance imaging study examined performance-matched cerebral activity during correct WM retrieval by balancing the mean number of correct responses as well as the mean response times between patients and controls and analyzing remaining correct trials. Forty-one schizophrenia patients and 41 healthy controls performed an event-related Sternberg task allowing for analysis of correctly remembered trials. Correct retrieval was associated with activation in a bilateral fronto-parieto-occipital network comprising mainly the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex and superior parietal cortex in controls and, to a weaker degree, in patients. Direct group comparison revealed significantly decreased activations in patients in the posterior (Brodmann area (BA) 31) and anterior (BA 32) cingulate cortex (ACC) and the medial caudate bilaterally when matching for performance. When matching for performance and response speed there was additional hypoactivation in the insula. Mean response times were negatively correlated with cingulate and caudate activation only in controls. Present findings suggest that during efficient WM retrieval processing patients exhibit only slightly impaired activation in a task-specific network containing mainly prefrontal and superior parietal areas. However, hypoactivation of areas predominantly responsible for cognitive control and response execution seems to remain even under performance-matched conditions. Given the relevant role of the caudate and the ACC in dopaminergically mediated executive processing, the results bear crucial implications for the psychopathology of schizophrenia.     

Share or compete? Load‐dependent recruitment of prefrontal cortex during dual‐task performance

Dual-task performance requires flexible attention allocation to two or more streams of information. Dorsolateral prefrontal cortex (DLPFC) is considered important for executive function, and recent modeling work proposes that attention control may arise from selective activation and inhibition of different processing units within this region. Here, we used a tone discrimination task and a visual letter memory task to examine whether this type of competition could be measurable using a neuroimaging technique, the event-related optical signal, with high spatial and temporal resolution. Left and right DLPFC structures were differentially affected by task priority and load, with the left middle frontal gyrus (MFG) being preferentially recruited by the visual memory task, whereas the two tasks competed for recruitment, in a spatially segregated manner, in right MFG. The data provide support for a competition view of dual-task processing.     

Socioaffective factors modulate working memory in schizophrenia patients

Working memory deficit in schizophrenia is a core cognitive feature of the disorder and is reliably associated with abnormalities of the prefrontal circuitry. Working memory deficits are also associated with impaired social functioning and present a major obstacle toward successful rehabilitation in schizophrenia. Although the role of prefrontal cortex in working memory has been extensively investigated, the intricate relations among the prefrontal circuitry, working memory and social behaviors are not clearly understood. In this study, we manipulated social context and observed its effects on spatial working memory. In experiment 1, the effects of social and asocial reinforcements on spatial working memory were examined in schizophrenic patients and healthy controls. The results show that social but not asocial reinforcements facilitated spatial working memory in schizophrenic patients. In experiment 2, the effects of human voice reinforcements (with or without affect) on working memory was investigated. Voice reinforcements did not facilitate working memory relative to the no-reinforcement condition. There was no difference between high-affect vs flat-affect voice conditions. In experiment 3, the effects of direct and indirect social interactions on spatial working memory were studied. Direct but not indirect social interaction facilitated working memory in schizophrenic patients. These results suggest that social context might facilitate working memory in schizophrenic patients perhaps by activating frontal lobe systems. In addition, the possibility of improving cognitive functions such as working memory using seemingly non-cognitive methods might lead to potential remediation strategies.     

健康人大脑和小脑空间记忆认知功能的fMRI研究

本研究应用功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,检测了健康人大脑和小脑参与空间记忆的认知过程。通过对10名右利手健康志愿者进行一项短时空间记忆任务作业的同时进行脑功能磁共振扫描,实验采用组块设计,任务与对照任务交替进行,数据采用SPM99软件进行数据分析和脑功能区定位。结果显示:当统计阈值设定为P<0.0001时,大脑皮层和右侧小脑一起被显著激活;大脑皮层所激活的脑区有双侧顶叶的楔前叶、顶上小叶、缘上回(BA7/40,BA:Brodma-nn Area),双侧前额上、中、下回(BA6/9/47),双侧枕叶和枕颞交界处(BA18/19/37),右侧海马回;左侧中脑黑质及被盖部也被激活。上述结果提示:小脑和大脑皮层一起参与了空间记忆的认知过程。     

Differentiated parietal connectivity of frontal regions for “what” and “where” memory

In a previous meta-analysis across almost 200 neuroimaging experiments, working memory for object location showed significantly stronger convergence on the posterior superior frontal gyrus, whereas working memory for identity showed stronger convergence on the posterior inferior frontal gyrus (dorsal to, but overlapping with Brodmann’s area BA 44). As similar locations have been discussed as part of a dorsal frontal—superior parietal reach system and an inferior frontal grasp system, the aim of the present study was to test whether the regions of working-memory related “what” and “where” processing show a similar distinction in parietal connectivity. The regions that were found in the previous meta-analysis were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modelling and task-independent resting state correlations. While the ventral seed showed significantly stronger connectivity with the bilateral intraparietal sulcus (IPS), the dorsal seed showed stronger connectivity with the bilateral posterior inferior parietal and the medial superior parietal lobule. The observed connections of regions involved in memory for object location and identity thus clearly demonstrate a distinction into separate pathways that resemble the parietal connectivity patterns of the dorsal and ventral premotor cortex in non-human primates and humans. It may hence be speculated that memory for a particular location and reaching towards it as well as object memory and finger positioning for manipulation may rely on shared neural systems. Moreover, the ensuing regions, in turn, featured differential connectivity with the bilateral ventral and dorsal extrastriate cortex, suggesting largely segregated bilateral connectivity pathways from the dorsal visual cortex via the superior and inferior parietal lobules to the dorsal posterior frontal cortex and from the ventral visual cortex via the IPS to the ventral posterior frontal cortex that may underlie action and cognition.