Distant Cortical Regions Research Articles

Role of dorsal striatum circuits in relapse to opioid seeking after voluntary abstinence

AbstractHigh relapse rate during abstinence is a defining characteristic of drug addiction. We previously found that opioid seeking progressively increases after voluntary abstinence induced by adverse consequences of oxycodone seeking (crossing an electric barrier). Functional MRI revealed that this effect is associated with changes in functional connectivity within medial orbitofrontal cortex (mOFC)- and dorsomedial striatum (DMS)-related circuits. Here, we used a pharmacological manipulation and fMRI to determine the causal role of mOFC and DMS in oxycodone seeking after electric barrier-induced abstinence. We trained rats to self-administer oxycodone (6 h/day, 14 days). Next, we induced voluntary abstinence by exposing them to an electric barrier for 2 weeks. We inactivated the mOFC and DMS with muscimol+baclofen (GABAa and GABAb receptor agonists) and then tested them for relapse to oxycodone seeking on abstinence days 1 or 15 without the electric barrier or oxycodone. Inactivation of DMS (p < 0.001) but not mOFC decreased oxycodone seeking before or after electric barrier-induced abstinence. Functional MRI data revealed that DMS inactivation decreased cerebral blood volume levels in DMS and several distant cortical and subcortical regions (corrected p < 0.05). Furthermore, functional connectivity of DMS with several frontal, sensorimotor, and auditory regions significantly increased after DMS inactivation (corrected p < 0.05). Finally, an exploratory analysis of an existing functional MRI dataset showed that DMS inactivation restored voluntary abstinence-induced longitudinal changes in DMS functional connectivity with these brain regions (p < 0.05). Results indicate a role of DMS and related brain circuits in oxycodone seeking after voluntary abstinence, suggesting potential targets for intervention.

ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum

Mutations in ARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms in humans. The most common structural abnormality in the brain of ARID1B patients is agenesis of the corpus callosum (ACC), characterized by the absence of an interhemispheric white matter tract that connects distant cortical regions. Here, we find that neurons expressing SATB2, a determinant of callosal projection neuron (CPN) identity, show impaired maturation in ARID1B+/- neural organoids. Molecularly, a reduction in chromatin accessibility of genomic regions targeted by TCF-like, NFI-like, and ARID-like transcription factors drives the differential expression of genes required for corpus callosum (CC) development. Through an invitro model of the CC tract, we demonstrate that this transcriptional dysregulation impairs the formation of long-range axonal projections, causing structural underconnectivity. Our study uncovers new functions of the mSWI/SNF during human corticogenesis, identifying cell-autonomous axonogenesis defects in SATB2+ neurons as a cause of ACC in ARID1B patients.

Cytoarchitectonic, receptor distribution and functional connectivity analyses of the macaque frontal lobe.

Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas, including novel subdivisions of Walker's areas 10, 9, 8B, and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Indeed, structural and functional organization of subdivisions encompassing areas 46 and 12 demonstrated significant differences in the interareal levels of α2 receptors. Furthermore, multivariate analysis included receptor fingerprints of previously identified 16 motor areas in the same macaque brains and revealed 5 clusters encompassing frontal lobe areas. We used the MRI datasets from the non-human primate data sharing consortium PRIME-DE to perform functional connectivity analyses using the resulting frontal maps as seed regions. In general, rostrally located frontal areas were characterized by bigger fingerprints, that is, higher receptor densities, and stronger regional interconnections. Whereas more caudal areas had smaller fingerprints, but showed a widespread connectivity pattern with distant cortical regions. Taken together, this study provides a comprehensive insight into the molecular structure underlying the functional organization of the cortex and, thus, reconcile the discrepancies between the structural and functional hierarchical organization of the primate frontal lobe. Finally, our data are publicly available via the EBRAINS and BALSA repositories for the entire scientific community.

Alterations in white matter integrity and network topological properties are associated with a decrease in global motion perception in older adults.

Previous studies have mainly explored the effects of structural and functional aging of cortical regions on global motion sensitivity in older adults, but none have explored the structural white matter (WM) substrates underlying the age-related decrease in global motion perception (GMP). In this study, random dot kinematogram and diffusion tensor imaging were used to investigate the effects of age-related reductions in WM fiber integrity and connectivity across various regions on GMP. We recruited 106 younger adults and 94 older adults and utilized both tract-based spatial statistics analysis and graph theoretical analysis to comprehensively investigate group differences in WM microstructural and network connections between older and younger adults at the microscopic and macroscopic levels. Moreover, partial correlation analysis was used to explore the relationship between alterations in WM and the age-related decrease in GMP. The results showed that decreased GMP in older adults was related to decreased fractional anisotropy (FA) of the inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, anterior thalamic radiation, superior longitudinal fasciculus, and cingulum cingulate gyrus. Decreased global efficiency of the WM structural network and increased characteristic path length were closely associated with decreased global motion sensitivity. These results suggest that the reduced GMP in older adults may stem from reduced WM integrity in specific regions of WM fiber tracts as well as decreased efficiency of information integration and communication between distant cortical regions, supporting the "disconnection hypothesis" of cognitive aging.

Functional Significance of Human Resting-State Networks Hubs Identified Using MEG During the Transition From Childhood to Adulthood.

Cortical hubs identified within resting-state networks (RSNs), areas of the cortex that have a higher-than-average number of connections, are known to be critical to typical cognitive functioning and are often implicated in disorders leading to abnormal cognitive functioning. Functionally defined cortical hubs are also known to change with age in the developing, maturing brain, mostly based on studies carried out using fMRI. We have recently used magnetoencephalography (MEG) to study the maturation trajectories of RSNs and their hubs from age 7 to 29 in 131 healthy participants with high temporal resolution. We found that maturation trajectories diverge as a function of the underlying cortical rhythm. Specifically, we found the beta band (13–30 Hz)-mediated RSNs became more locally efficient with maturation, i.e., more organized into clusters and connected with nearby regions, while gamma (31–80 Hz)-mediated RSNs became more globally efficient with maturation, i.e., prioritizing faster signal transmission between distant cortical regions. We also found that different sets of hubs were associated with each of these networks. To better understand the functional significance of this divergence, we wanted to examine the cortical functions associated with the identified hubs that grew or shrunk with maturation within each of these networks. To that end, we analyzed the results of the prior study using Neurosynth, a platform for large-scale, automated synthesis of fMRI data that links brain coordinates with their probabilistically associated terms. By mapping the Neurosynth terms associated with each of these hubs, we found that maturing hubs identified in the gamma band RSNs were more likely to be associated with bottom-up processes while maturing hubs identified in the beta band RSNs were more likely to be associated with top-down functions. The results were consistent with the idea that beta band-mediated networks preferentially support the maturation of top-down processing, while the gamma band-mediated networks preferentially support the maturation of bottom-up processing.

Temporally and functionally distinct large-scale brain network dynamics supporting task switching

ObjectiveOur daily activities require frequent switches among competing responses at the millisecond time scale. We determined the spatiotemporal characteristics and functional significance of rapid, large-scale brain network dynamics during task switching. MethodsThis cross-sectional study investigated patients with drug-resistant focal epilepsy who played a Lumosity cognitive flexibility training game during intracranial electroencephalography (iEEG) recording. According to a given task rule, unpredictably switching across trials, participants had to swipe the screen in the direction the stimulus was pointing or moving. Using this data, we described the spatiotemporal characteristics of iEEG high-gamma augmentation occurring more intensely during switch than repeat trials, unattributable to the effect of task rule (pointing or moving), within-stimulus congruence (the direction of stimulus pointing and moving was same or different in a given trial), or accuracy of an immediately preceding response. Diffusion-weighted imaging (DWI) tractography determined whether distant cortical regions showing enhanced activation during task switch trials were directly connected by white matter tracts. Trial-by-trial iEEG analysis deduced whether the intensity of task switch-related high-gamma augmentation was altered through practice and whether high-gamma amplitude predicted the accuracy of an upcoming response among switch trials. ResultsThe average number of completed trials during five-minute gameplay was 221.4 per patient (range: 171–285). Task switch trials increased the response times, whereas later trials reduced them. Analysis of iEEG signals sampled from 860 brain sites effectively elucidated the distinct spatiotemporal characteristics of task switch, task rule, and post-error-specific high-gamma modulations. Post-cue, task switch-related high-gamma augmentation was initiated in the right calcarine cortex after 260 ms, right precuneus after 330 ms, right entorhinal after 420 ms, and bilateral anterior middle-frontal gyri after 450 ms. DWI tractography successfully showed the presence of direct white matter tracts connecting the right visual areas to the precuneus and anterior middle-frontal regions but not between the right precuneus and anterior middle-frontal regions. Task-related high-gamma amplitudes in later trials were reduced in the calcarine, entorhinal and anterior middle-frontal regions, but increased in the precuneus. Functionally, enhanced post-cue precuneus high-gamma augmentation improved the accuracy of subsequent responses among switch trials. ConclusionsOur multimodal analysis uncovered two temporally and functionally distinct network dynamics supporting task switching. High-gamma augmentation in the visual-precuneus pathway may reflect the neural process facilitating an attentional shift to a given updated task rule. High-gamma activity in the visual-dorsolateral prefrontal pathway, rapidly reduced through practice, may reflect the cost of executing appropriate stimulus-response translation.

Excitatory-Inhibitory Homeostasis and Diaschisis: Tying the Local and Global Scales in the Post-stroke Cortex.

Maintaining a balance between excitatory and inhibitory activity is an essential feature of neural networks of the neocortex. In the face of perturbations in the levels of excitation to cortical neurons, synapses adjust to maintain excitatory-inhibitory (EI) balance. In this review, we summarize research on this EI homeostasis in the neocortex, using stroke as our case study, and in particular the loss of excitation to distant cortical regions after focal lesions. Widespread changes following a localized lesion, a phenomenon known as diaschisis, are not only related to excitability, but also observed with respect to functional connectivity. Here, we highlight the main findings regarding the evolution of excitability and functional cortical networks during the process of post-stroke recovery, and how both are related to functional recovery. We show that cortical reorganization at a global scale can be explained from the perspective of EI homeostasis. Indeed, recovery of functional networks is paralleled by increases in excitability across the cortex. These adaptive changes likely result from plasticity mechanisms such as synaptic scaling and are linked to EI homeostasis, providing a possible target for future therapeutic strategies in the process of rehabilitation. In addition, we address the difficulty of simultaneously studying these multiscale processes by presenting recent advances in large-scale modeling of the human cortex in the contexts of stroke and EI homeostasis, suggesting computational modeling as a powerful tool to tie the meso- and macro-scale processes of recovery in stroke patients.

Altered microstructural properties of superficial white matter in patients with Parkinson's disease.

Parkinson's disease (PD), a chronic neurodegenerative disease, is characterized by sensorimotor and cognitive deficits. Previous diffusion tensor imaging (DTI) studies found abnormal DTI metrics in white matter bundles, such as the corpus callosum, cingulate, and frontal-parietal bundles, in PD patients. These studies mainly focused on alterations in microstructural features of long-range bundles within the deep white matter (DWM) that connects pairs of distant cortical regions. However, less is known about the DTI metrics of the superficial white matter (SWM) that connects local cortical regions in PD patients. To determine whether the DTI metrics of the SWM were different between the PD patients and the healthy controls, we recruited DTI data from 34 PD patients and 29 gender- and age-matched healthy controls. Using a probabilistic tractographic approach, we first defined a population-based SWM mask across all the subjects. Using a tract-based spatial statistical (TBSS) analytic approach, we then identified the SWM bundles showing abnormal DTI metrics in the PD patients. We found that the PD patients showed significantly lower DTI metrics in the SWM bundles connecting the sensorimotor cortex, cingulate cortex, posterior parietal cortex (PPC), and parieto-occipital cortex than the healthy controls. We also found that the clinical measures in the PD patients was significantly negatively correlated with the fractional anisotropy in the SWM (FASWM) that connects core regions in the default mode network (DMN). The FASWM in the bundles that connected the PPC was significantly positively correlated with cognitive performance in the PD patients. Our findings suggest that SWM may serve as the brain structural basis underlying the sensorimotor deficits and cognitive degeneration in PD patients.

How cerebral cortex protects itself from interictal spikes: The alpha/beta inhibition mechanism.

Interactions between interictal epileptiform discharges (IEDs) and distant cortical regions subserve potential effects on cognition of patients with focal epilepsy. We hypothesize that “healthy” brain areas at a distance from the epileptic focus may respond to the interference of IEDs by generating inhibitory alpha and beta oscillations. We predict that more prominent alpha‐beta oscillations can be found in patients with less impaired neurocognitive profile. We performed a source imaging magnetoencephalography study, including 41 focal epilepsy patients: 21 with frontal lobe epilepsy (FLE) and 20 with mesial temporal lobe epilepsy. We investigated the effect of anterior (i.e., frontal and temporal) IEDs on the oscillatory pattern over posterior head regions. We compared cortical oscillations (5–80 Hz) temporally linked to 3,749 IEDs (1,945 frontal and 1,803 temporal) versus an equal number of IED‐free segments. We correlated results from IED triggered oscillations to global neurocognitive performance. Only frontal IEDs triggered alpha‐beta oscillations over posterior head regions. IEDs with higher amplitude triggered alpha‐beta oscillations of higher magnitude. The intensity of posterior head region alpha‐beta oscillations significantly correlated with a better neuropsychological profile. Our study demonstrated that cerebral cortex protects itself from IEDs with generation of inhibitory alpha‐beta oscillations at distant cortical regions. The association of more prominent oscillations with a better cognitive status suggests that this mechanism might play a role in determining the cognitive resilience in patients with FLE.

Spatial convergence of distant cortical regions during folding explains why arteries do not cross the sylvian fissure.

Cortical folding places regions that are separated by a large distance along the cortical surface in close proximity. This process is not homogeneous; regions such as the insular opercula have a much higher cortical surface distance (CSD) to euclidean distance (ED) than others. Here the authors explore the hypothesis that in the folded brain the CSD, and not the ED, determines regions of common irrigation, because this measure corresponds more closely with the distance along the prefolded brain, where the subarachnoid arterial vascular network starts forming. The authors defined a convergence index that compared the ED to the CSD and applied it to the cortical surface reconstruction of an average brain. They then compared cortical convergence to the irrigation patterns of major sulci and fissures of the brain, by assessing whether these structures were crossed or not crossed by arterial vessels in 20 fixed hemispheres. The regions of highest convergence (top 1%) were clustered around the sylvian fissure, which is the only brain depression with high convergence values along its edges. Arterial crossings were commonly observed in every major sulcus of the brain, with the exception of the sylvian fissure, constituting a highly significant difference (p < 10-4). Arteries do not cross regions of high convergence. In the adult brain the CSD, rather than the ED, predicts the regional irrigation pattern. The distant origin of the frontal and temporal lobes creates a region of high cortical convergence, which explains why arteries do not cross the sylvian fissure.

Functional and Structural Network Disorganizations in Typical Epilepsy With Centro-Temporal Spikes and Impact on Cognitive Neurodevelopment.

Epilepsy with Centrotemporal Spikes (ECTS) is the most common form of self-limited focal epilepsy. The pathophysiological mechanisms by which ECTS induces neuropsychological impairment in 15–30% of affected children remain unclear. The objective of this study is to review the current state of knowledge concerning the brain structural and functional changes that may be involved in cognitive dysfunctions in ECTS. Structural brain imaging suggests the presence of subtle neurodevelopmental changes over the epileptogenic zone and over distant regions in ECTS. This structural remodeling likely occurs prior to the diagnosis and evolves over time, especially in patients with cognitive impairment, suggesting that the epileptogenic processes might interfere with the dynamics of the brain development and/or the normal maturation processes. Functional brain imaging demonstrates profound disorganization accentuated by interictal epileptic spikes (IES) in the epileptogenic zone and in remote networks in ECTS. Over the epileptogenic zone, the literature demonstrates changes in term of neuronal activity and synchronization, which are effective several hundred milliseconds before the IES. In the same time window, functional changes are also observed in bilateral distant networks, notably in the frontal and temporal lobes. Effective connectivity demonstrates that the epileptogenic zone constitutes the key area at the origin of IES propagation toward distant cortical regions, including frontal areas. Altogether, structural and functional network disorganizations, in terms of: (i) power spectral values, (ii) functional and effective connectivity, are likely to participate in the cognitive impairment commonly reported in children with ECTS. These results suggest a central and causal role of network disorganizations related to IES in the neuropsychological impairment described in ECTS children.

The varied semiology of seizures in the context of small anterior temporal encephaloceles.

Small encephaloceles of the anterior temporal pole have been increasingly recognised as an underlying epileptogenic substrate in patients with medically refractory epilepsy. The current report aims to expand on the current knowledge by emphasising that seizure semiology in such patients can vary significantly. Patients were selected from an epilepsy surgery database between 2012 and 2017. Of the 143 patients who underwent epilepsy surgery, six patients had a temporal encephalocele. Four of these patients had stereo-EEG implantation. Of the four patients studied, each had a seizure semiology discordant with an ictal focus in the temporal lobe. Intracranial EEG assessment demonstrated, irrespective of this semiology, seizures originated from the anterior temporal pole. Seizures were observed to rapidly propagate to the orbitofrontal cortex, insula, temporo-occipital junction, and posterior language regions. Engagement of the mesial temporal structures could occur early or late, however, a good surgical outcome was achieved following a focused lesionectomy in either situation. The major finding was that seizures arising from anterior temporal encephaloceles can have an extra-temporal semiology. The varied clinical semiology and the rapid propagation to seemingly distant cortical regions could be explained by the connectivity of the anterior temporal lobe.

Functional and structural network disorganizations in typical ECTS and impact on cognitive neurodevelopment

Background Epilepsy with Centrotemporal Spikes (ECTS) is the most common form of self-limited focal epilepsy. The pathophysiological mechanisms by which ECTS induces neuropsychological impairment in 30% of affected children remain unclear. Objectives The objective is to review the current state of knowledge concerning the brain structural and functional changes that may be involved in cognitive dysfunctions in ECTS. Methods Publication indexed in Pubmed about structural and functional brain imaging in ECTS were reviewed. Results Structural brain imaging suggests the presence of subtle neurodevelopmental changes over the epileptogenic zone (EZ) and over distant regions, which evolves over time, especially in patients with cognitive impairment. This suggests that the epileptogenic processes might interfere with the dynamics of the brain development. Functional brain imaging demonstrates disorganization accentuated by IES. Changes in neuronal activity are described several hundred milliseconds before the IES in over the EZ and in bilateral distant networks. This is associated with alteration of global small-world properties towards a more random network. The direction of information flow demonstrates that, the epileptogenic zone constitutes the key area at the origin of IES propagation towards distant cortical regions. Conclusion Structural and functional network disorganizations, in terms of: (i) power spectral values, (ii) functional and effective connectivity, are likely to participate in the cognitive impairment reported in children with ECTS. These results suggest a central and causal role of network disorganizations related to IES in the neuropsychological impairment.

Cortical atrophy and transcallosal diaschisis following isolated subcortical stroke

Following acute ischemic stroke, isolated subcortical lesions induce gray matter atrophy in anatomically connected, yet distant cortical brain regions. We expand on previous studies by analyzing cortical thinning in contralesional, homologous regions indirectly linked to primary stroke lesions via ipsilesional cortical areas. For this purpose, stroke patients were serially studied by magnetic resonance imaging (diffusion tensor imaging and high-resolution anatomical imaging) in the acute (days 3–5) and late chronic stage one year after stroke. We analyzed changes of gray and white matter integrity in 18 stroke patients (median age 68 years) with subcortical stroke. We applied probabilistic fiber tractography to identify brain regions connected to stroke lesions and contralesional homologous areas. Cortical thickness was quantified by semi-automatic measurements, and fractional anisotropy was analyzed. One year after stroke, significant decrease of cortical thickness was detected in areas connected to ischemic lesions (mean −0.15 mm; 95% CI −0.23 to −0.07 mm) as well as homologous contralateral brain regions (mean −0.13 mm; 95% CI −0.07 to −0.19 mm). We detected reduced white matter integrity of inter- and intrahemispheric fiber tracts. There were no significant associations with clinical recovery. Our results indicate that impact of subcortical lesions extends to homologous brain areas via transcallosal diaschisis.

Post-Encoding Amygdala-Visuosensory Coupling Is Associated with Negative Memory Bias in Healthy Young Adults.

The amygdala is well documented as the critical nexus of emotionally enhanced memory, yet its role in the creation of negative memory biases, better memory for negative compared with positive stimuli, has not been clarified. Although prior work suggests valence-specific effects at the moment of "online" encoding and retrieval, with enhanced visuosensory processes supporting negative memories in particular, here we tested the novel hypothesis that the amygdala engages with distant cortical regions after encoding in a manner that predicts inter-individual differences in negative memory biases in humans. Twenty-nine young adults (males and females) were scanned while they incidentally encoded negative, neutral, and positive scenes, each preceded by a line-drawing sketch of the scene. Twenty-four hours later, participants were scanned during an Old/New recognition memory task with only the line-drawings presented as retrieval cues. We replicated and extended our prior work, showing that enhanced online visuosensory recapitulation supports negative memory. Critically, resting-state scans flanked the encoding task, allowing us to show for the first time that individual differences in "off-line" increases in amygdala resting-state functional connectivity (RSFC) immediately following encoding relate to negative and positive memory bias at test. Specifically, post-encoding increases in amygdala RSFC with visuosensory and frontal regions were associated with the degree of negative and positive memory bias, respectively. These findings provide new evidence that valence-specific negative memory biases can be linked to the way that sensory processes are integrated into amygdala-centered emotional memory networks.SIGNIFICANCE STATEMENT Decades of research has placed the amygdala at the center of the emotional memory network. Despite the clinical importance of disproportionate memory for negative compared with positive events, it is not known whether post-encoding increases in amygdala-cortical coupling, possibly reflective of early consolidation processes, bear any influence on the degree or direction of such emotional memory biases. We demonstrate that, across participants, increases in post-encoding amygdala coupling with visuosensory and frontal regions are associated with more pronounced negative and positive memory biases, respectively. These findings provide the first evidence linking post-encoding amygdala modulation to the degree of negative or positive memory bias, emphasizing the need for valence-based accounts of the amygdala's role in emotional memory.

Detecting Large-Scale Brain Networks Using EEG: Impact of Electrode Density, Head Modeling and Source Localization

Resting state networks (RSNs) in the human brain were recently detected using high-density electroencephalography (hdEEG). This was done by using an advanced analysis workflow to estimate neural signals in the cortex and to assess functional connectivity (FC) between distant cortical regions. FC analyses were conducted either using temporal (tICA) or spatial independent component analysis (sICA). Notably, EEG-RSNs obtained with sICA were very similar to RSNs retrieved with sICA from functional magnetic resonance imaging data. It still remains to be clarified, however, what technological aspects of hdEEG acquisition and analysis primarily influence this correspondence. Here we examined to what extent the detection of EEG-RSN maps by sICA depends on the electrode density, the accuracy of the head model, and the source localization algorithm employed. Our analyses revealed that the collection of EEG data using a high-density montage is crucial for RSN detection by sICA, but also the use of appropriate methods for head modeling and source localization have a substantial effect on RSN reconstruction. Overall, our results confirm the potential of hdEEG for mapping the functional architecture of the human brain, and highlight at the same time the interplay between acquisition technology and innovative solutions in data analysis.

Hypothalamic hamartoma: Epileptogenesis beyond the lesion?

The discovery of intrinsic epileptogenicity of the hypothalamic hamartoma (HH) marked a new area in understanding the associated clinical syndrome, often manifesting as progressive epileptic encephalopathy. However, therapeutic procedures targeting the HH proved to be inefficient to cure seizures in up to 50% of cases, whereas in cases with partial improvement, the electroclinical patterns of persisting seizures suggest an involvement of distant cortical regions. The concept of kindling-like secondary epileptogenesis has been suggested as a possible underlying mechanism. Yet the role of the hypothalamic lesion in the pathophysiology of the syndrome remains debatable. In the Strasbourg-Kork series, the best outcomes were obtained when the duration of epilepsy before endoscopic HH surgery did not exceed 10years. In two patients with HH ablation followed at a later time by a temporal lobectomy, only this second surgical step allowed complete seizure freedom. These findings suggest the existence of an independent, third stage of secondary epileptogenesis in human. In the Grenoble series, stereotactic intracerebral recordings (stereo electroencephalography [SEEG]) of five HH cases demonstrated that gelastic/dacrystic seizures were correlated with discharges within the HH, whereas other seizure types were related to discharges affecting cortical regions, which sometimes seemed to be triggered by HH. In the Marseille series, two cases explored by SEEG provided evidence of extended epileptogenicity outside the limits of the HH, forming complex epileptogenic networks, with HH still triggering clusters of neocortical seizures in the first, but not obligatory involved in spontaneous seizures in the second case. Taken together, our data argue for the existence of dynamic ictal network organization, with possible "kindling-like" relationships between the HH and the neocortex or widespread epileptogenesis. Despite the existence of secondary epileptogenesis, the epileptogenic zone could still be limited to the hamartoma, for which early surgical treatment should be pragmatically considered as a first surgical step.

Dynamic causal modelling revisited

This paper revisits the dynamic causal modelling of fMRI timeseries by replacing the usual (Taylor) approximation to neuronal dynamics with a neural mass model of the canonical microcircuit. This provides a generative or dynamic causal model of laminar specific responses that can generate haemodynamic and electrophysiological measurements. In principle, this allows the fusion of haemodynamic and (event related or induced) electrophysiological responses. Furthermore, it enables Bayesian model comparison of competing hypotheses about physiologically plausible synaptic effects; for example, does attentional modulation act on superficial or deep pyramidal cells – or both? In this technical note, we describe the resulting dynamic causal model and provide an illustrative application to the attention to visual motion dataset used in previous papers. Our focus here is on how to answer long-standing questions in fMRI; for example, do haemodynamic responses reflect extrinsic (afferent) input from distant cortical regions, or do they reflect intrinsic (recurrent) neuronal activity? To what extent do inhibitory interneurons contribute to neurovascular coupling? What is the relationship between haemodynamic responses and the frequency of induced neuronal activity? This paper does not pretend to answer these questions; rather it shows how they can be addressed using neural mass models of fMRI timeseries.

Physical Exercise Preserves Adult Visual Plasticity in Mice and Restores it after a Stroke in the Somatosensory Cortex.

The primary visual cortex (V1) is widely used to study brain plasticity, which is not only crucial for normal brain function, such as learning and memory, but also for recovery after brain injuries such as stroke. In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in V1 declines with age and is compromised by a lesion in adjacent and distant cortical regions. In contrast, mice raised in an enriched environment (EE), exhibit lifelong OD plasticity and are protected from losing OD plasticity after a stroke-lesion in the somatosensory cortex. Since SC mice with an access to a running wheel (RW) displayed preserved OD plasticity during aging, we investigated whether physical exercise might also provide a plasticity promoting effect after a cortical stroke. To this end, we tested if adult RW-raised mice preserved OD plasticity after stroke and also if short-term running after stroke restored OD plasticity to SC mice. Indeed, unlike mice without a RW, adult RW mice continued to show OD plasticity even after stroke, and a 2 weeks RW experience after stroke already restored lost OD plasticity. Additionally, the experience-enabled increase of the spatial frequency and contrast threshold of the optomotor reflex of the open eye, normally lost after a stroke, was restored in both groups of RW mice. Our data suggest that physical exercise alone can not only preserve visual plasticity into old age, but also restore it after a cortical stroke.

Extrinsic origins of the somatostatin and neuropeptide Y innervation of the rat basolateral amygdala

The amygdalar basolateral nuclear complex (BLC) is a cortex-like structure that receives inputs from many cortical areas. It has long been assumed that cortico-amygdalar projections, as well as inter-areal intracortical connections, arise from cortical pyramidal cells. However, recent studies have shown that GABAergic long-range nonpyramidal neurons (LRNP neurons) in the cortex also contribute to inter-areal connections. The present study combined Fluorogold (FG) retrograde tract tracing with immunohistochemistry for cortical nonpyramidal neuronal markers to determine if cortical LRNP neurons project to the BLC in the rat. Injections of FG into the BLC produced widespread retrograde labeling in the cerebral hemispheres and diencephalon. Triple-labeling for FG, somatostatin (SOM), and neuropeptide Y (NPY) revealed a small number of FG+/SOM+/NPY+ neurons and FG+/SOM+/NPY− neurons in the lateral entorhinal area, amygdalopiriform transition area, and piriform cortex, but not in the prefrontal and insular cortices, or in the diencephalon. In addition, FG+/SOM+/NPY+ neurons were observed in the amygdalostriatal transition area and in a zone surrounding the intercalated nuclei. About half of the SOM+ neurons in the lateral entorhinal area labeled by FG were GABA+. FG+ neurons containing parvalbumin were only seen in the basal forebrain, and no FG+ neurons containing vasoactive intestinal peptide were observed in any brain region. Since LRNP neurons involved in corticocortical connections are critical for synchronous oscillations that allow temporal coordination between distant cortical regions, the LRNP neurons identified in this study may play a role in the synchronous oscillations of the BLC and hippocampal region that are involved in the retrieval of fear memories.