Reduced thalamic resting‐state functional connectivity and impaired cognition in acute abstinent heroin users

As a critical component of cortico‐striato‐thalamo‐cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting‐state functional connectivity (RSFC) differences of the thalamus were investigated between age‐, gender‐, and alcohol‐matched 37 HU and 33 healthy controls (HCs). Trail making test‐A (TMT‐A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT‐A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU.     

Resting state functional connectivity of the subthalamic nucleus in Parkinson's disease assessed using arterial spin‐labeled perfusion fMRI

Neurophysiological changes within the cortico‐basal ganglia‐thalamocortical circuits appear to be a characteristic of Parkinson's disease (PD) pathophysiology. The subthalamic nucleus (STN) is one of the basal ganglia components showing pathological neural activity patterns in PD. In this study, perfusion imaging data, acquired noninvasively using arterial spin‐labeled (ASL) perfusion MRI, were used to assess the resting state functional connectivity (FC) of the STN in 24 early‐to‐moderate PD patients and 34 age‐matched healthy controls, to determine whether altered FC in the very low frequency range of the perfusion time signal occurs as a result of the disease. Our results showed that the healthy STN was functionally connected with other nuclei of the basal ganglia and the thalamus, as well as with discrete cortical areas including the insular cortex and the hippocampus. In PD patients, connectivity of the STN was increased with two cortical areas involved in motor and cognitive processes. These findings suggest that hyperconnectivity of the STN could underlie some of the motor and cognitive deficits often present even at early stages of the disease. The FC measures provided good discrimination between controls and patients, suggesting that ASL‐derived FC metrics could be a putative PD biomarker. Hum Brain Mapp 36:1937–1950, 2015. © 2015 Wiley Periodicals, Inc .     

The role of sleep on cognition and functional connectivity in patients with multiple sclerosis

Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC.     

The cortico-basal ganglia integrative network: the role of the thalamus

The thalamus is a critical component of the frontal cortical-basal ganglia-thalamic circuits that mediate motivation and emotional drive, planning and cognition for the development and expression of goal-directed behaviors. Each functional region of the frontal cortex is connected with specific areas of each basal ganglia (BG) structure and of the thalamus. In addition, the thalamus sends a massive, topographically organized projection directly to the striatum. Tract-tracing and physiological experiments have indicated a general topographic organization of the cortical-BG-thalamic loops and supported a model of BG function based on parallel and segregated pathways. However, the learning and execution of appropriate behavioral responses require integration of inputs related to emotional, cognitive, and motor cortical functions. Our recent data indicate that integration may occur via non-reciprocal connections between the striatum and substantia nigra and within "hot spots" of convergence between corticostriatal projections from different functional regions. Similarly, integration may exist in the thalamus. There are non-reciprocal connections between the thalamus and cortex via thalamocortical projections that terminate in the superficial and deep cortical layers. These terminals can influence different functional cortical areas that, in turn, project to the striatum and back to the thalamus. In addition, a non-reciprocal corticothalamic projection terminates in thalamic regions that are parts of other circuits. Finally, 'hot spots' of convergence between terminals from different cortical regions may also occur in the thalamus as is seen in the striatum. Thus, via several different pathways, the thalamus may serve as an important center of integration of networks that underlie the ability to modulate behaviors.     

Functional integrity of thalamocortical circuits differentiates normal aging from mild cognitive impairment

Resonance in thalamocortical networks is critically involved in sculpting oscillatory behavior in large ensembles of neocortical cells. Neocortical oscillations provide critical information about the integrity of thalamocortical circuits and functional connectivity of cortical networks, which seem to be significantly disrupted by the neuronal death and synapse loss characterizing Alzheimer's disease (AD). By applying a novel analysis methodology to overcome volume conduction effects between scalp electroencephalographic (EEG) measurements, we were able to estimate the temporal activation of EEG‐alpha sources in the thalamus and parieto‐occipital regions of the cortex. We found that synaptic flow underlying the lower alpha band (7.5–10 Hz) was abnormally facilitated in patients with mild cognitive impairment (MCI) as compared to healthy elderly individuals, particularly from thalamus to cortex (～38% higher). In addition, the thalamic generator of lower alpha oscillations was also abnormally activated in patients with MCI. Regarding the upper alpha subdivision (10.1–12.5 Hz), both controls and patients with MCI showed a bidirectional decrease of thalamocortical synaptic transmission, which was age‐dependent only in the control group. Altogether, our results suggest that functional dynamics of thalamocortical networks differentiate individuals at high risk of developing AD from healthy elderly subjects, supporting the hypothesis that neurodegeneration mechanisms are active years before the patient is clinically diagnosed with dementia. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Functional and structural alterations of dorsal attention network in preclinical and early-stage Alzheimer's disease

Objectives

Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are known as the preclinical and early stage of Alzheimer's disease (AD). The dorsal attention network (DAN) is mainly responsible for the “top-down” attention process. However, previous studies mainly focused on single functional modality and limited structure. This study aimed to investigate the multimodal alterations of DAN in SCD and aMCI to assess their diagnostic value in preclinical and early-stage AD.

Methods

Resting-state functional magnetic resonance imaging (MRI) was carried out to measure the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC). Structural MRI was used to calculate the gray matter volume (GMV) and cortical thickness. Moreover, receiver-operating characteristic (ROC) analysis was used to distinguish these alterations in SCD and aMCI.

Results

The SCD and aMCI groups showed both decreased ReHo in the right middle temporal gyrus (MTG) and decreased GMV compared to healthy controls (HCs). Especially in the SCD group, there were increased fALFF and increased ReHo in the left inferior occipital gyrus (IOG), decreased fALFF and increased FC in the left inferior parietal lobule (IPL), and reduced cortical thickness in the right inferior temporal gyrus (ITG). Furthermore, functional and structural alterations in the SCD and aMCI groups were closely related to episodic memory (EM), executive function (EF), and information processing speed (IPS). The combination of multiple indicators of DAN had a high accuracy in differentiating clinical stages.

Conclusions

Our current study demonstrated functional and structural alterations of DAN in SCD and aMCI, especially in the MTG, IPL, and SPL. Furthermore, cognitive performance was closely related to these significant alterations. Our study further suggested that the combined multiple indicators of DAN could be acted as the latent neuroimaging markers of preclinical and early-stage AD for their high diagnostic value.     

Structural connectivity‐defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations

In spite of the well‐known importance of thalami in multiple sclerosis (MS), only limited data on whole and subregional thalamic functional connectivity (FC) changes are available. Using diffusion tensor imaging, we performed a structural connectivity based thalamic parcellation and investigated subregional thalamic resting‐state (RS) FC alterations and their relationship with clinical/cognitive measures in MS. MRI data from a reference set of healthy controls (HC) were used to parcellate the thalami into five subregions, according to their structural connectivity. For each thalamic subregion, a seed‐based RS FC analysis was performed in 187 MS patients and 94 HC. Correlations between thalamic RS FC and clinical/cognitive variables were assessed. Compared to HC, MS patients showed increased intra‐ and inter‐thalamic RS FC for almost all thalamic subregions, and increased RS FC between all thalamic subregions and the left insula. Frontal and motor thalamic subregions also showed reduced RS FC with the caudate nucleus. For the temporal thalamic subregion, we observed reduced RS FC with the ipsilateral thalamus, anterior and middle cingulate cortex, and cerebellum. Compared to cognitively preserved, cognitively impaired MS patients had higher thalamic RS FC with several temporal areas. In MS patients, lower RS FC between thalamic subregions and the caudate and cingulate cortex correlated with worse motor performance, whereas higher RS FC with the insula correlated with better motor performance. The main thalamic subregions have different RS‐FC abnormalities in MS patients. Increased thalamic RS FC with the insula may have a compensatory role, whereas increased RS FC with temporal areas, observed in patients with cognitive impairment may reflect maladaptive mechanisms. Hum Brain Mapp 38:6005–6018, 2017. © 2017 Wiley Periodicals, Inc.     

长期海洛因成瘾者前额叶功能连接的静息态fMRI研究

目的 利用静息态fMRI探讨长期海洛因成瘾者前额叶功能连接的变化情况.方法 13例长期海洛因成瘾者和14例正常者接受静息态fMRI检查,对数据进行相关的预处理后,以前额叶为种子点与全脑每个体素进行相关分析,比较海洛因成瘾组与正常对照组前额叶功能连接的变化情况.结果 以左侧前额叶为种子点进行功能连接分析,海洛因成瘾组左侧前额叶与左侧海马、右侧前扣带回、左侧额中回、右侧额中回、右侧楔前叶功能连接明显低于正常对照组:以右侧前额叶为种子点进行功能连接分析,海洛因成瘾组右侧前额叶与左侧眶额叶、左侧额中回功能连接明显低于正常对照组.结论 长期海洛因成瘾者前额叶与相关脑区的功能连接减弱,前额叶可能参与了海洛因成瘾的维持与戒断后复吸.

Abstract：

Objective To explore the changes of functional connectivity of the prefrontal cortex in chronic heroin addicts under resting-state functional MRI (fMRI). Methods Resting fMRI examination was performed on 13 chronic heroin addicts and 14 healthy volunteers. After pre-processing the resting-state fMRI data, the prefrontal cortex was selected as the seed region, with which a whole-brain voxel temporal correlation in Iow frequency fMRI fluctuations was analyzed and the changes of functional connectivity of the prefrontal lobe in both chronic heroin addicts and healthy volunteers were calculated with SPM5 software. Results Compared with that in the control group, the functional connectivity between the left prefrontal cortex and the left hippocampus, right anterior cingulate, left middle frontal gyrus, right middle frontal gyrus, right precuneus in the heroin addiction group was significantly decreased. The functional connectivity between the right prefrontal cortex and the left orbital frontal cortex, left middle frontal gyrus in thc heroin addiction group was also significantly decreased as compared with that in the control group. Conclusion Functional connectivity of prefrontal cortex in chronic heroin addicts decreases, indicating that the prefrontal cortex may be involved in the maintenance of heroin addiction and relapse after withdrawal.     

Structural and functional connectivity of the precuneus and thalamus to the default mode network

Neuroimaging studies have identified functional interactions between the thalamus, precuneus, and default mode network (DMN) in studies of consciousness. However, less is known about the structural connectivity of the precuneus and thalamus to regions within the DMN. We used diffusion tensor imaging (DTI) to parcellate the precuneus and thalamus based on their probabilistic white matter connectivity to each other and DMN regions of interest (ROIs) in 37 healthy subjects from the Human Connectome Database. We further assessed resting‐state functional connectivity (RSFC) among the precuneus, thalamus, and DMN ROIs. The precuneus was found to have the greatest structural connectivity with the thalamus, where connection fractional anisotropy (FA) increased with age. The precuneus also showed significant structural connectivity to the hippocampus and middle pre‐frontal cortex, but minimal connectivity to the angular gyrus and midcingulate cortex. In contrast, the precuneus exhibited significant RSFC with the thalamus and the strongest RSFC with the AG. Significant symmetrical structural connectivity was found between the thalamus and hippocampus, mPFC, sFG, and precuneus that followed known thalamocortical pathways, while thalamic RSFC was strongest with the precuneus and hippocampus. Overall, these findings reveal high levels of structural and functional connectivity linking the thalamus, precuneus, and DMN. Differences between structural and functional connectivity (such as between the precuneus and AG) may be interpreted to reflect dynamic shifts in RSFC for cortical hub‐regions involved with consciousness, but could also reflect the limitations of DTI to detect superficial white matter tracts that connect cortico‐cortical regions. Hum Brain Mapp 38:938–956, 2017. © 2016 Wiley Periodicals, Inc.     

Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy

It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is currently unknown which thalamic nuclei and how nuclear‐specific thalamocortical functional connectivity are differentially impacted in patients with medically refractory and non‐refractory idiopathic generalised epilepsy (IGE). In the present study, we performed structural and resting‐state functional magnetic resonance imaging (MRI) in patients with refractory and non‐refractory IGE, segmented the thalamus into constituent nuclear regions using a probabilistic MRI segmentation method and determined thalamocortical functional connectivity using seed‐to‐voxel connectivity analyses. We report significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory IGE. Compared to healthy controls, patients with refractory and non‐refractory IGE had significant alterations of functional connectivity between the centromedian nucleus and cortex, but only patients with refractory IGE had altered cortical connectivity with the ventral lateral nuclear group. Patients with refractory IGE had significantly increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to patients with non‐refractory IGE. Cortical effects were predominantly located in the frontal lobe. Atrophy of the anterior thalamic nuclei and resting‐state functional hyperconnectivity between ventral lateral nuclei and cerebral cortex may be imaging markers of pharmacoresistance in patients with IGE. These structural and functional abnormalities fit well with the known importance of thalamocortical systems in the generation and maintenance of primary generalised seizures, and the increasing recognition of the importance of limbic pathways in IGE.     

Neural correlates of substance abuse: Reduced functional connectivity between areas underlying reward and cognitive control

Substance use disorders (SUD) have been associated with dysfunction in reward processing, habit formation, and cognitive‐behavioral control. Accordingly, neurocircuitry models of addiction highlight roles for nucleus accumbens, dorsal striatum, and prefrontal/anterior cingulate cortex. However, the precise nature of the disrupted interactions between these brain regions in SUD, and the psychological correlates thereof, remain unclear. Here we used magnetic resonance imaging to measure rest‐state functional connectivity of three key striatal nuclei (nucleus accumbens, dorsal caudate, and dorsal putamen) in a sample of 40 adult male prison inmates (n = 22 diagnosed with SUD; n = 18 without SUD). Relative to the non‐SUD group, the SUD group exhibited significantly lower functional connectivity between the nucleus accumbens and a network of frontal cortical regions involved in cognitive control (dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and frontal operculum). There were no group differences in functional connectivity for the dorsal caudate or dorsal putamen. Moreover, the SUD group exhibited impairments in laboratory measures of cognitive‐behavioral control, and individual differences in functional connectivity between nucleus accumbens and the frontal cortical regions were related to individual differences in measures of cognitive‐behavioral control across groups. The strength of the relationship between functional connectivity and cognitive control did not differ between groups. These results indicate that SUD is associated with abnormal interactions between subcortical areas that process reward (nucleus accumbens) and cortical areas that govern cognitive‐behavioral control. Hum Brain Mapp 35:4282–4292, 2014. © 2014 Wiley Periodicals, Inc .     

Altered functional network architecture in orbitofronto‐striato‐thalamic circuit of unmedicated patients with obsessive‐compulsive disorder

Dysfunction of corticostriatal loops has been proposed to underlie certain cognitive and behavioral problems associated with various neuropsychiatric disorders, such as obsessive‐compulsive disorder (OCD) characterized by repetitive, unwanted thoughts, and behaviors. Although functional abnormalities in the loops involving the orbitofronto‐striato‐thalamic (OFST) circuitry in patients with OCD have been reported, our understanding of a link between disruptions in the architecture of the intrinsic functional network of the OFST circuit and their symptoms remain incomplete. Using resting‐state functional MRI in conjunction with unsupervised clustering and multilevel functional connectivity (FC) techniques, FC of the OFST network and its topological organization in 61 OCD patients versus 61 matched controls were characterized. Patients exhibited disruptions in small‐world properties of the OFST circuit, which indicates an imbalance between functional integration and segregation. Patients also showed decreased FC between the central orbitofrontal cortex and dorsomedial striatum but increased FC between the medial thalamus and striatal areas. Using one of the largest samples of unmedicated OCD patients to date, our findings provide evidence supporting the OFST dysconnection hypothesis in OCD as a basic pathophysiological mechanism underlying the disorder, showing the disruption of FC between specific cortical, striatal, and thalamic clusters and aberrant topological patterns of the OFST circuit. Hum Brain Mapp 38:109–119, 2017. © 2016 Wiley Periodicals, Inc.     

The primate mediodorsal (MD) nucleus and its projection to the frontal lobe

The frontal lobe projections of the mediodorsal (MD) nucleus of the thalamus were examined in rhesus monkey by transport of retrograde markers injected into one of nine cytoarchitectonic regions (Walker's areas 6, 8A, 9, 10, 11, 12, 13, 46, and Brodmann's area 4) located in the rostral third of the cerebrum. Each area of prefrontal, premotor, or motor cortex injected was found to receive a topographically unique thalamic input from clusters of cells in specific subdivisions within MD. All of the prefrontal areas examined also receive topographically organized inputs from other thalamic nuclei including, most prominently, the ventral anterior (VA) and medial pulvinar nuclei. Conversely, and in agreement with previous findings, MD projects to areas of the frontal lobe beyond the traditional borders of prefrontal cortex, such as the anterior cingulate and supplementary motor cortex. The topography of thalamocortical neurons revealed in coronal sections through VA, MD, and pulvinar is circumferential. In the medial part of MD, for example, thalamocortical neurons shift from a dorsal to a ventral position for cortical targets lying medial to lateral along the ventral surface of the lobe; neurons in the lateral MD move from a ventral to a dorsal position, for cortical areas situated lateral to medial on the convexity of the hemisphere. The aggregate evidence for topographic specificity is supported further by experiments in which different fluorescent dyes were placed in multiple areas of the frontal lobe in each of three cases. The results show that very few, if any, thalamic neurons project to more than one area of cortex. The widespread cortical targets of MD neurons together with evidence for multiple thalamic inputs to prefrontal areas support a revision of the classical hodological definition of prefrontal cortex as the exclusive cortical recipient of MD projections. Rather, the prefrontal cortex is defined by multiple specific relationships with the thalamus.     

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

The focus of this literature review is on the three interacting brain areas that participate in decision‐making: basal ganglia, ventral motor thalamic nuclei, and medial prefrontal cortex, with an emphasis on the participation of the ventromedial and ventral anterior motor thalamic nuclei in prefrontal cortical function. Apart from a defining input from the mediodorsal thalamus, the prefrontal cortex receives inputs from ventral motor thalamic nuclei that combine to mediate typical prefrontal functions such as associative learning, action selection, and decision‐making. Motor, somatosensory and medial prefrontal cortices are mainly contacted in layer 1 by the ventral motor thalamic nuclei and in layer 3 by thalamocortical input from mediodorsal thalamus. We will review anatomical, electrophysiological, and behavioral evidence for the proposed participation of ventral motor thalamic nuclei and medial prefrontal cortex in rat and mouse motor decision‐making.     

Abnormal resting‐state functional connectivity of the nucleus accumbens in multi‐year abstinent heroin addicts

Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross‐sectional study, whole‐brain resting‐state functional magnetic resonance images (8 min) were collected from 30 heroin‐addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting‐state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse‐related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin‐dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long‐term‐abstinent heroin‐dependent individuals. © 2015 Wiley Periodicals, Inc.     

Alterations of resting‐state fMRI measurements in individuals with cervical dystonia

Cervical dystonia (CD) is a neurological disorder with typical symptoms of involuntary and abnormal movements and postures of the head. CD‐associated alterations of functional brain networks have not been well characterized. Previous studies of CD using resting‐state functional MRI (rfMRI) are limited in two aspects: (i) the analyses were not directly focused on the functional brain network related to head movement and (ii) rfMRI measurements other than functional connectivity (FC) were not investigated. The present study examined alterations of FC in CD by capitalizing on newly identified brain regions supporting isometric head rotation (Prudente et al.: J Neurosci 35 (2015) 9163–9172). In addition to FC, which only reflects inter‐regional signal synchronization, local, or intraregional alterations were also examined using rfMRI measurements of the fractional amplitude of low‐frequency fluctuations and regional homogeneity (ReHo). Finally, with alterations of different rfMRI measures identified, a support vector machine (SVM) learning algorithm was implemented for group classification. The results revealed both inter‐ (FC) and intra‐regional (ReHo) alterations extensively distributed in both cortical and subcortical structures; and common alterations of these measures were identified bilaterally in the postcentral gyrus as well as in the basal ganglia and thalamus. Of the rfMRI features examined, seven of them (four FC and three ReHo measures) survived the SVM procedure of recursive feature elimination and together provided the highest group classification accuracy of 90.6%. The present findings extend previous studies of rfMRI in CD and offer insight into the underlying pathophysiology of the disorder in relation to network dysfunction and somatosensory disturbances. Hum Brain Mapp 38:4098–4108, 2017. © 2017 Wiley Periodicals, Inc.     

Post-traumatic stress influences local and remote functional connectivity: a resting-state functional magnetic resonance imaging study

Post-traumatic stress disorder (PTSD) is associated with alterations in regional brain activation and remote functional connectivity (FC) in limbic and prefrontal cortex. However, little is known about local FC changes following a traumatic event. Resting-state functional magnetic resonance images were collected for typhoon survivors with (n = 27) and without PTSD (n = 33), and healthy controls (n = 30). Local FC was examined by calculating regional homogeneity (ReHo), and remote FC was investigated between regions showing significant ReHo group differences. The PTSD group showed ReHo changes in multiple regions, including the amygdala, parahippocampal gyrus, and prefrontal cortex relative to both control groups. Compared with healthy controls, typhoon survivors had increased ReHo in the insula/inferior frontal gyrus, middle and dorsal anterior cingulate cortex (MCC/dACC), as well as enhanced negative FC between the MCC/dACC and posterior cingulate cortex (PCC)/precuneus. The typhoon-exposed control group exhibited higher ReHo in the PCC/precuneus than the PTSD and healthy control groups. Furthermore, positive correlations were found between PTSD symptom severity and ReHo in several regions. Post-traumatic stress can influence local and remote FC, irrespective of PTSD diagnosis. Future studies are needed to validate the findings and to determine whether the alterations represent pre-existing or acquired deficits.     

Cortical connections of the lateral mediodorsal thalamus in cynomolgus monkeys

The prefrontal cortex has been defined as that cortical territory that has "essential or sustaining" connections with the mediodorsal (MD) nucleus of the thalamus. However, recent studies in the monkey have documented projections from MD to the more caudal, agranular regions of the frontal cortex, suggesting that the connections of MD may be characterized by a breadth of distribution and diversity of functional roles too great to be useful as a unifying and defining feature for a specific cortical territory. In this study, we placed tracer injections in the lateral divisions of MD in cynomolgus monkeys (Macaca fascicularis) to assess the relative proportions of connections devoted to diverse regions of the frontal cortex (FC). Three different patterns of label were observed in the cortex, associated with different locations within lateral MD. We have designated these as the ventrolateral MD-arcuate FC circuit, having most label in areas 8 and 6; the caudoventral MD-dorsomedial FC circuit, having most label in areas 24 and presupplementary motor area (SMA); and the anterodorsal MD-anterior FC circuit, with the most label in areas 9, 46, 12, and 10. Only two of the nine cases injected in lateral MD were predominantly connected with the anterior FC. Thus, particular locales within lateral MD are connected with multiple, functionally diverse cortical regions, including several not classically recognized as "prefrontal" areas. This divergence may distinguish MD-frontocortical and reciprocal corticothalamic pathways from the largely segregated pathways arising from the other thalamic nuclei that are interconnected with the frontal cortex, such as those from the ventrolateral nuclear group.     

Formation of specific afferent connections in organotypic slice cultures from rat visual cortex cocultured with lateral geniculate nucleus.

The development of the cerebral cortex involves the specification of intrinsic circuitry and extrinsic connections, the pattern of inputs and outputs. To investigate the development of a major afferent input to the cortex, we studied the formation of thalamocortical connections in an organotypic culture system. Slices from the lateral thalamus of young rats were cocultured with slices from the visual cortex. Thalamocortical projections in vitro were examined anatomically with fluorescent dyes and physiologically with electrophysiological and optical recording techniques. Axons emerged from thalamic explants radially in all directions. The outgrowth of thalamic fibers and the course of the axonal trajectories were not influenced by the presence of the cocultured cortex. Only those thalamic axons that happened to grow toward the cortical slices invaded their target tissue. Thalamocortical projection cell in vitro had the characteristic morphology of thalamic relay neurons. Cells with the morphology of interneurons were present in thalamic explants, but these neurons did not project to the cocultured cortex. Thalamocortical axons in vitro terminated in their appropriate cortical target layer, formed axonal arbors, and made functional synaptic contacts. Such specific connections between thalamic neurons and their cortical target cells were established regardless of whether thalamocortical axons invaded the cortex from the white matter side or from the pial surface. These results suggest that thalamic projection neurons have an innate mechanism that allows them to recognize their cortical target cells. Thus, intrinsic factors play a significant role in the laminar specification of cortical connections during development.     

Altered intra- and interregional synchronization in the absence of the corpus callosum: a resting-state fMRI study

Agenesis of the corpus callosum (AgCC) can result in subtle to severe cognitive deficits. Individuals with impaired cognition often show abnormalities on resting-state functional magnetic resonance imaging (rs-fMRI). This study used rs-fMRI to investigate changes in regional homogeneity (ReHo) and functional connectivity (FC) among individuals with AgCC. AgCC individuals (n = 10) and age-, sex-, and education-matched healthy control subjects (n = 19) were included in this study. The ReHo values were calculated to represent spontaneous brain activity. The regions which showed altered ReHo were selected as seeds to compare FC with the whole brain between the AgCC group and the healthy control group. Compared with healthy control subjects, the AgCC individuals had increased ReHo in the left anterior cingulate gyrus, left rolandic operculum, and right precuneus and decreased ReHo in the right calcarine, right cingual gyrus and right cuneus gyrus. The right calcarine and the right lingual gyrus in the AgCC exhibited decreased FC with bilateral cuneus, superior occipital gyrus, Rolandic operculum, superior temporal gyrus, posterior central gyrus, and midcingulate gyrus.The right cuneus gyrus in the AgCC individuals exhibited decreased FC with the bilateral calcarine gyrus, left cuneus, and left superior occipital gyrus. Our study revealed several subareas within the visual cortex exhibited remarkable abnormalities of spontaneous brain activity and decreased FC with the higher-order cognitive cortex.The abnormalities of ReHo and FC in AgCC individuals may provide new insights into the neurological pathophysiology.