Postoperative axonal changes in the contralateral hemisphere in children with medically refractory epilepsy: A longitudinal diffusion tensor imaging connectome analysis

To determine brain plasticity changes due to resective epilepsy surgery in children, we performed a longitudinal connectome analysis on the pattern of axonal connectivity in the contralateral hemisphere. Pre‐ and postoperative diffusion tensor imaging (DTI) data were acquired from 35 children with intractable focal epilepsy. A total of 54 brain regions of interest (ROIs) were generated in the hemisphere contralateral to the resection. Within a 54 × 54 connectivity matrix, a pairwise connectivity score was calculated for each connection between two ROIs, based on the DTI fiber streamline number in each connection. A permuted Spearman's ρ‐rank analysis was used to identify specific inter‐regional connections showing a significant association between the postoperative change of connectivity score and clinical variables. Nineteen connections in the contralateral hemisphere showed postoperative increases in the strength of connectivity. Postoperative increase in connectivity between insular–inferior frontal operculum regions as well as that between superior frontal orbital and mid frontal orbital regions were both significantly associated with a larger surgical resection volume (ρ > +0.40) and a younger patient age (ρ > ?0.34). These increases were more robust in patients with frontal resection and in those achieving seizure freedom. Neuropsychological evaluation on subsets of patients revealed that such increases in connectivity were associated with preserved or improved cognitive functions such as visual memory and planning. Resective epilepsy surgery may lead to increased contralateral axonal connectivity in children with focal epilepsy. Our data lead to a hypothesis that such increased connectivity may be an imaging marker of postoperative brain plasticity to compensate for cognitive function. Hum Brain Mapp 37:3946–3956, 2016. © 2016 Wiley Periodicals, Inc.     

Altered anterior‐posterior connectivity through the arcuate fasciculus in temporal lobe epilepsy

How the interactions between cortices through a specific white matter pathway change during cognitive processing in patients with epilepsy remains unclear. Here, we used surface‐based structural connectivity analysis to examine the change in structural connectivity with Broca's area/the right Broca's homologue in the lateral temporal and inferior parietal cortices through the arcuate fasciculus (AF) in 17 patients with left temporal lobe epilepsy (TLE) compared with 17 healthy controls. Then, we investigated its functional relevance to the changes in task‐related responses and task‐modulated functional connectivity with Broca's area/the right Broca's homologue during a semantic classification task of a single word. The structural connectivity through the AF pathway and task‐modulated functional connectivity with Broca's area decreased in the left midtemporal cortex. Furthermore, task‐related response decreased in the left mid temporal cortex that overlapped with the region showing a decrease in the structural connectivity. In contrast, the region showing an increase in the structural connectivity through the AF overlapped with the regions showing an increase in task‐modulated functional connectivity in the left inferior parietal cortex. These structural and functional changes in the overlapping regions were correlated. The results suggest that the change in the structural connectivity through the left frontal–temporal AF pathway underlies the altered functional networks between the frontal and temporal cortices during the language‐related processing in patients with left TLE. The left frontal–parietal AF pathway might be employed to connect anterior and posterior brain regions during language processing and compensate for the compromised left frontal–temporal AF pathway. Hum Brain Mapp 37:4425–4438, 2016. © 2016 Wiley Periodicals, Inc.     

Broca’s region: linking human brain functional connectivity data and non‐human primate tracing anatomy studies

Brodmann areas 6, 44 and 45 in the ventrolateral frontal cortex of the left hemisphere of the human brain constitute the anterior language production zone. The anatomical connectivity of these areas with parietal and temporal cortical regions was recently examined in an autoradiographic tract‐tracing study in the macaque monkey. Studies suggest strong correspondence between human resting state functional connectivity (RSFC) based on functional magnetic resonance imaging data and experimentally demonstrated anatomical connections in non‐human primates. Accordingly, we hypothesized that areas 6, 44 and 45 of the human brain would exhibit patterns of RSFC consistent with patterns of anatomical connectivity observed in the macaque. In a primary analysis, we examined the RSFC associated with regions‐of‐interest placed in ventrolateral frontal areas 6, 44 and 45, on the basis of local sulcal and gyral anatomy. We validated the results of the primary hypothesis‐driven analysis with a data‐driven partitioning of ventrolateral frontal cortex into regions exhibiting distinct RSFC patterns, using a spectral clustering algorithm. The RSFC of ventrolateral frontal areas 6, 44 and 45 was consistent with patterns of anatomical connectivity shown in the macaque. We observed a striking dissociation between RSFC for the ventral part of area 6 that is involved in orofacial motor control and RSFC associated with Broca’s region (areas 44 and 45). These findings indicate rich and differential RSFC patterns for the ventrolateral frontal areas controlling language production, consistent with known anatomical connectivity in the macaque brain, and suggest conservation of connectivity during the evolution of the primate brain.     

Monkey to human comparative anatomy of the frontal lobe association tracts

The greater expansion of the frontal lobes along the phylogeny scale has been interpreted as the signature of evolutionary changes underlying higher cognitive abilities in humans functions in humans. However, it is unknown how an increase in number of gyri, sulci and cortical areas in the frontal lobe have coincided with a parallel increase in connectivity. Here, using advanced tractography based on spherical deconvolution, we produced an atlas of human frontal association connections that we compared with axonal tracing studies of the monkey brain. We report several similarities between human and monkey in the cingulum, uncinate, superior longitudinal fasciculus, frontal aslant tract and orbito-polar tract. These similarities suggest to preserved functions across anthropoids. In addition, we found major differences in the arcuate fasciculus and the inferior fronto-occipital fasciculus. These differences indicate possible evolutionary changes in the connectional anatomy of the frontal lobes underlying unique human abilities.     

Functional topography of the right inferior parietal lobule structured by anatomical connectivity profiles

The nature of the relationship between structure and function is a fundamental question in neuroscience, especially at the macroscopic neuroimaging level. Although mounting studies have revealed that functional connectivity reflects structural connectivity, whether similar structural and functional connectivity patterns can reveal corresponding similarities in the structural and functional topography remains an open problem. In our current study, we used the right inferior parietal lobule (RIPL), which has been demonstrated to have similar anatomical and functional connectivity patterns at the subregional level, to directly test the hypothesis that similar structural and functional connectivity patterns can inform the corresponding topography of this area. In addition, since the association between the RIPL regions and particular functions and networks is still largely unknown, post‐hoc functional characterizations and connectivity analyses were performed to identify the main functions and cortical networks in which each subregion participated. Anatomical and functional connectivity‐based parcellations of the RIPL have consistently identified five subregions. Our functional characterization using meta‐analysis‐based behavioral and connectivity analyses revealed that the two anterior subregions (Cl1 and Cl2) primarily participate in interoception and execution, respectively; whereas the posterior subregion (Cl3) in the SMG primarily participates in attention and action inhibition. The two posterior subregions (Cl4, Cl5) in the AG were primarily involved in social cognition and spatial cognition, respectively. These results indicated that similar anatomical and functional connectivity patterns of the RIPL are reflected in corresponding structural and functional topographies. The identified cortical connectivity and functional characterization of each subregion may facilitate RIPL‐related clinical research. Hum Brain Mapp 37:4316–4332, 2016. © 2016 Wiley Periodicals, Inc.     

Connectivity of an effective hypothalamic surgical target for cluster headache.

The purpose of this study was to look at the connectivity of the posterior inferior hypothalamus in a patient implanted with a deep brain stimulating electrode using probabilistic tractography in conjunction with postoperative MRI scans. In a patient with chronic cluster headache we implanted a deep brain stimulating electrode into the ipsilateral postero-medial hypothalamus to successfully control his pain. To explore the connectivity, we used the surgical target from the postoperative MRI scan as a seed for probabilistic tractography, which was then linked to diffusion weighted imaging data acquired in a group of healthy control subjects. We found highly consistent connections with the reticular nucleus and cerebellum. In some subjects, connections were also seen with the parietal cortices, and the inferior medial frontal gyrus. Our results illustrate important anatomical connections that may explain the functional changes associated with cluster headaches and elucidate possible mechanisms responsible for triggering attacks.     

Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition

Recent evidence shows that task‐deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task‐deactivated brain regions ‐ usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task‐activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally‐directed and internally‐focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli.     

New insights in the homotopic and heterotopic connectivity of the frontal portion of the human corpus callosum revealed by microdissection and diffusion tractography

Extensive studies revealed that the human corpus callosum (CC) plays a crucial role in providing large–scale bi‐hemispheric integration of sensory, motor and cognitive processing, especially within the frontal lobe. However, the literature lacks of conclusive data regarding the structural macroscopic connectivity of the frontal CC. In this study, a novel microdissection approach was adopted, to expose the frontal fibers of CC from the dorsum to the lateral cortex in eight hemispheres and in one entire brain. Post‐mortem results were then combined with data from advanced constrained spherical deconvolution in 130 healthy subjects. We demonstrated as the frontal CC provides dense inter‐hemispheric connections. In particular, we found three types of fronto‐callosal fibers, having a dorso‐ventral organization. First, the dorso‐medial CC fibers subserve homotopic connections between the homologous medial cortices of the superior frontal gyrus. Second, the ventro‐lateral CC fibers subserve homotopic connections between lateral frontal cortices, including both the middle frontal gyrus and the inferior frontal gyrus, as well as heterotopic connections between the medial and lateral frontal cortices. Third, the ventro‐striatal CC fibers connect the medial and lateral frontal cortices with the contralateral putamen and caudate nucleus. We also highlighted an intricate crossing of CC fibers with the main association pathways terminating in the lateral regions of the frontal lobes. This combined approach of ex vivo microdissection and in vivo diffusion tractography allowed demonstrating a previously unappreciated three‐dimensional architecture of the anterior frontal CC, thus clarifying the functional role of the CC in mediating the inter‐hemispheric connectivity. Hum Brain Mapp 37:4718–4735, 2016. © 2016 Wiley Periodicals, Inc.     

Sensory and semantic category subdivisions within the anterior temporal lobes

In the semantic memory literature the anterior temporal lobe (ATL) is frequently discussed as one homogeneous region when in fact, anatomical studies indicate that it is likely that there are discrete subregions within this area. Indeed, the influential Hub Account of semantic memory has proposed that this region is a sensory-amodal, general-purpose semantic processing region. However review of the literature suggested two potential demarcations: sensory subdivisions and a social/nonsocial subdivision. To test this, participants were trained to associate social or non-social words with novel auditory, visual, or audiovisual stimuli. Later, study participants underwent an fMRI scan where they were presented with the sensory stimuli and the task was to recall the semantic associate. The results showed that there were sensory specific subdivisions within the ATL - that the perceptual encoding of auditory stimuli preferentially activated the superior ATL, visual stimuli the inferior ATL, and multisensory stimuli the polar ATL. Moreover, our data showed that there is stimulus-specific sensitivity within the ATL - the superior and polar ATLs were more sensitive to the retrieval of social knowledge as compared to non-social knowledge. No ATL regions were more sensitive to the retrieval of non-social knowledge. These findings indicate that the retrieval of newly learned semantic associations activates the ATL. In addition, superior and polar aspects of the ATL are sensitive to social stimuli but relatively insensitive to non-social stimuli, a finding that is predicted by anatomical connectivity and single-unit studies in non-human primates. And lastly, the ATL contains sensory processing subdivisions that fall along superior (auditory), inferior (visual), polar (audiovisual) subdivisions.     

Fascículos asociativos ínsulo-operculares: revisión de su anatomía y de las implicaciones para el abordaje transopercular a la ínsula

IntroductionThe insula is a highly connected area, as an intricate network of afferent and efferent projections connect it with adjacent and distant cortical regions.ObjectiveTo perform an extensive review of recent literature to analyse the anatomy of the associative tracts related to the insula.ResultsThe frontal aslant tract, arcuate fasciculus, horizontal portion of the superior longitudinal fasciculus and the middle longitudinal fasciculus are associative tracts connected to the opercula. The inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus run under the anterior and inferior portion of the insula.Conclusionsthe pars triangularis and orbicularis of the inferior frontal gyrus, as well as the middle and anterior part of the superior temporal gyrus, have few connections with the perisylvian associative network. Consequently, in the trans-opercular approach to the insula, these 2 regions represent anatomical corridors that give access to the insula. The IFOF and the uncinate fasciculus represent the deep functional margin of resection.     

Altered resting‐state connectivity during interictal generalized spike‐wave discharges in drug‐naïve childhood absence epilepsy

Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike‐wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE). Methods: The EEG‐functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drug‐naïve CAE, and three different brain networks—the default mode network (DMN), cognitive control network (CCN), and affective network (AN)—were investigated. Results: Cross‐correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus‐dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC‐inferior frontal junction (IFJ), and pre‐supplementary motor area (pre‐SMA) subregions connectivity disruption in CCN; ACC‐ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusions: The current findings demonstrate significant alterations of resting‐state networks in drug naïve CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro‐pathophysiological mechanism of psychosocial function impairments in patients with CAE. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Perisylvian language networks of the human brain

Early anatomically based models of language consisted of an arcuate tract connecting Broca's speech and Wernicke's comprehension centers; a lesion of the tract resulted in conduction aphasia. However, the heterogeneous clinical presentations of conduction aphasia suggest a greater complexity of perisylvian anatomical connections than allowed for in the classical anatomical model. This article re-explores perisylvian language connectivity using in vivo diffusion tensor magnetic resonance imaging tractography. Diffusion tensor magnetic resonance imaging data from 11 right-handed healthy male subjects were averaged, and the arcuate fasciculus of the left hemisphere reconstructed from this data using an interactive dissection technique. Beyond the classical arcuate pathway connecting Broca's and Wernicke's areas directly, we show a previously undescribed, indirect pathway passing through inferior parietal cortex. The indirect pathway runs parallel and lateral to the classical arcuate fasciculus and is composed of an anterior segment connecting Broca's territory with the inferior parietal lobe and a posterior segment connecting the inferior parietal lobe to Wernicke's territory. This model of two parallel pathways helps explain the diverse clinical presentations of conduction aphasia. The anatomical findings are also relevant to the evolution of language, provide a framework for Lichtheim's symptom-based neurological model of aphasia, and constrain, anatomically, contemporary connectionist accounts of language.     

Default network connectivity during a working memory task

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task‐related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task‐related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task‐positive networks at rest. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Brain structure associations with phonemic and semantic fluency in typically-developing children

Verbal fluency is the ability to retrieve lexical knowledge quickly and efficiently and develops during childhood and adolescence. Few studies have investigated associations between verbal fluency performance and brain structural variation in children. Here we examined associations of verbal fluency performance with structural measures of frontal and temporal language-related brain regions and their connections in 73 typically-developing children aged 7–13 years. Tract-based spatial statistics was used to extract fractional anisotropy (FA) from the superior longitudinal fasciculus/arcuate fasciculus (SLF/AF), and the white matter underlying frontal and temporal language-related regions. FreeSurfer was used to extract cortical thickness and surface area. Better semantic and phonemic fluency performance was associated with higher right SLF/AF FA, and phonemic fluency was also modestly associated with lower left SLF/AF FA. Explorative voxelwise analyses for semantic fluency suggested associations with FA in other fiber tracts, including corpus callosum and right inferior fronto-occipital fasciculus. Overall, our results suggest that verbal fluency performance in children may rely on right hemisphere structures, possibly involving both language and executive function networks, and less on solely left hemisphere structures as often is observed in adults. Longitudinal studies are needed to clarify whether these associations are mediated by maturational processes, stable characteristics and/or experience.     

Significance of longitudinal changes in the default‐mode network for cognitive recovery after stroke

Although a considerable number of patients suffer from cognitive impairments after stroke, the neural mechanism of cognitive recovery has not yet been clarified. Repeated resting‐state functional magnetic resonance imaging (fMRI) was used in this study to examine longitudinal changes in the default‐mode network (DMN) during the 6 months after stroke, and to investigate the relationship between DMN changes and cognitive recovery. Out of 24 initially recruited right‐hemispheric stroke patients, 11 (eight males, mean age 55.7 years) successfully completed the repeated fMRI protocol. Patients underwent three fMRI sessions at 1, 3 and 6 months after stroke. Their DMNs were analysed and compared with those of 11 age‐matched healthy subjects (nine males, mean age 56.2 years). Correlations between DMN connectivity and improvement of the cognitive performance scores were also assessed. The stroke patients were found to demonstrate markedly decreased DMN connectivity of the posterior cingulate cortex, precuneus, medial frontal gyrus and inferior parietal lobes at 1 month after stroke. At 3 months after stroke, the DMN connectivity of these brain areas was almost restored, suggesting that the period is critical for neural reorganization. The DMN connectivity of the dorsolateral prefrontal cortex in the contralesional hemisphere showed a significant correlation with cognitive function recovery in stroke patients, and should be considered a compensatory process for overcoming cognitive impairment due to brain lesion. This is the first longitudinal study to demonstrate the changes in DMN during recovery after stroke and the key regions influencing cognitive recovery.     

Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia

Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract‐based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Transcallosal connection patterns of opposite dorsal premotor regions support a lateralized specialization for action and perception

Lateralization of higher brain functions requires that a dominant hemisphere collects relevant information from both sides. The right dorsal premotor cortex (PMd), particularly implicated in visuomotor transformations, was hypothesized to be optimally located to converge visuospatial information from both hemispheres for goal‐directed movement. This was assessed by probabilistic tractography and a novel analysis enabling group comparisons of whole‐brain connectivity distributions of the left and right PMd in standard space (16 human subjects). The resulting dominance of contralateral PMd connections was characterized by right PMd connections with left visual and parietal areas, indeed supporting a dominant role in visuomotor transformations, while the left PMd showed dominant contralateral connections with the frontal lobe. Ipsilateral right PMd connections were also stronger with posterior parietal regions, relative to the left PMd connections, while ipsilateral connections of the left PMd were stronger with, particularly, the anterior cingulate, the ventral premotor and anterior parietal cortex. The pattern of dominant right PMd connections thus points to a specific role in guiding perceptual information into the motor system, while the left PMd connections are consistent with action dominance based on a lead in motor intention and fine precision skills.     

Insight and psychosis: Functional and anatomical brain connectivity and self‐reflection in Schizophrenia

Impaired insight into illness, associated with worse treatment outcome, is common in schizophrenia. Insight has been related to the self‐reflective processing, centred on the medial frontal cortex. We hypothesized that anatomical and functional routes to and from the ventromedial prefrontal cortex (vmPFC) would differ in patients according to their degree of impaired insight. Forty‐five schizophrenia patients and 19 healthy subjects performed a self‐reflection task during fMRI, and underwent diffusion tensor imaging. Using dynamic causal modelling we observed increased effective connectivity from the posterior cingulate cortex (PCC), inferior parietal lobule (IPL), and dorsal mPFC (dmPFC) towards the vmPFC with poorer insight and decrease from vmPFC to the IPL. Stronger connectivity from the PCC to vmPFC during judgment of traits related to self was associated with poorer insight. We found small‐scale significant changes in white matter integrity associated with clinical insight. Self‐reflection may be influenced by synaptic changes that lead to the observed alterations in functional connectivity accompanied by the small‐scale but measurable alterations in anatomical connections. Our findings may point to a neural compensatory response to an impairment of connectivity between self‐processing regions. Similarly, the observed hyper‐connectivity might be a primary deficit linked to inefficiency in the component cognitive processes that lead to impaired insight. We suggest that the stronger cognitive demands placed on patients with poor insight is reflected in increased effective connectivity during the task in this study. Hum Brain Mapp 36:4859–4868, 2015. © 2015 Wiley Periodicals, Inc .     

The effects of hippocampal lesions on MRI measures of structural and functional connectivity

Focal lesions can affect connectivity between distal brain regions (connectional diaschisis) and impact the graph‐theoretic properties of major brain networks (connectomic diaschisis). Given its unique anatomy and diverse range of functions, the hippocampus has been claimed to be a critical “hub” in brain networks. We investigated the effects of hippocampal lesions on structural and functional connectivity in six patients with amnesia, using a range of magnetic resonance imaging (MRI) analyses. Neuropsychological assessment revealed marked episodic memory impairment and generally intact performance across other cognitive domains. The hippocampus was the only brain structure exhibiting reduced grey‐matter volume that was consistent across patients, and the fornix was the only major white‐matter tract to show altered structural connectivity according to both diffusion metrics. Nonetheless, functional MRI revealed both increases and decreases in functional connectivity. Analysis at the level of regions within the default‐mode network revealed reduced functional connectivity, including between nonhippocampal regions (connectional diaschisis). Analysis at the level of functional networks revealed reduced connectivity between thalamic and precuneus networks, but increased connectivity between the default‐mode network and frontal executive network. The overall functional connectome showed evidence of increased functional segregation in patients (connectomic diaschisis). Together, these results point to dynamic reorganization following hippocampal lesions, with both decreased and increased functional connectivity involving limbic‐diencephalic structures and larger‐scale networks. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

A transcallosal fibre system between homotopic inferior frontal regions supports complex linguistic processing

Inferior frontal regions in the left and right hemisphere support different aspects of language processing. In the canonical model, left inferior frontal regions are mostly involved in processing based on phonological, syntactic and semantic features of language, whereas the right inferior frontal regions process paralinguistic aspects like affective prosody. Using diffusion tensor imaging (DTI)‐based probabilistic fibre tracking in 20 healthy volunteers, we identify a callosal fibre system connecting left and right inferior frontal regions that are involved in linguistic processing of varying complexity. Anatomically, we show that the interhemispheric fibres are highly aligned and distributed along a rostral to caudal gradient in the body and genu of the corpus callosum to connect homotopic inferior frontal regions. In the light of converging data, taking previous DTI‐based tracking studies and clinical case studies into account, our findings suggest that the right inferior frontal cortex not only processes paralinguistic aspects of language (such as affective prosody), as purported by the canonical model, but also supports the computation of linguistic aspects of varying complexity in the human brain. Our model may explain patterns of right‐hemispheric contribution to stroke recovery as well as disorders of prosodic processing. Beyond language‐related brain function, we discuss how inter‐species differences in interhemispheric connectivity and fibre density, including the system we described here may also explain differences in transcallosal information transfer and cognitive abilities across different mammalian species.