Effects of Early and Late Bilingualism on Resting-State Functional Connectivity.

Of current interest is how variations in early language experience shape patterns of functional connectivity in the human brain. In the present study, we compared simultaneous (two languages from birth) and sequential (second language learned after age 5 years) bilinguals using a seed-based resting-state MRI approach. We focused on the inferior frontal gyrus (IFG) as our ROI, as recent studies have demonstrated both neurofunctional and neurostructural changes related to age of second language acquisition in bilinguals in this cortical area. Stronger functional connectivity was observed for simultaneous bilinguals between the left and right IFG, as well as between the inferior frontal gyrus and brain areas involved in language control, including the dorsolateral prefrontal cortex, inferior parietal lobule, and cerebellum. Functional connectivity between the left IFG and the right IFG and right inferior parietal lobule was also significantly correlated with age of acquisition for sequential bilinguals; the earlier the second language was acquired, the stronger was the functional connectivity. In addition, greater functional connectivity between homologous regions of the inferior frontal gyrus was associated with reduced neural activation in the left IFG during speech production. The increased connectivity at rest and reduced neural activation during task performance suggests enhanced neural efficiency in this important brain area involved in both speech production and domain-general cognitive processing. Together, our findings highlight how the brain's intrinsic functional patterns are influenced by the developmental timeline in which second language acquisition occurs. SIGNIFICANCE STATEMENT: Of current interest is how early life experience leaves its footprint on brain structure and function. In this regard, bilingualism provides an optimal way to determine the effects of the timing of language learning because a second language can be learned from birth or later in life. We used resting-state fMRI to look at simultaneous and sequential bilinguals who differed only in age of acquisition, and found stronger connectivity between language and cognitive control regions in bilinguals who learned their two languages simultaneously, a pattern that was associated with more efficient brain activation during speech. Our findings highlight how functional connections in the brain differ depending upon when learning takes place.

Stability of resting state networks in the female brain during hormonal changes and their relation to premenstrual symptoms.

Resting-state fMRI is a promising imaging technique to evaluate functions in the human brain in health and disease. Different hormonal stages of the female menstrual cycle and hormonal contraceptives use affect results in task-based fMRI; it is however not yet clarified whether resting state networks are also altered. A population of 18 women with a natural cycle, and 19 women using hormonal contraceptives was examined in a longitudinal study-design. The natural cycle group was scanned at 3 time-points (follicular phase, ovulation, luteal phase), and the contraceptives group was scanned twice (inactive pill-phase, active pill-phase). Blood samples were acquired to evaluate hormonal concentrations, and premenstrual symptoms were assessed through daily record of severity of problems questionnaires. Results show no major alterations in the default mode network and the executive control network between different hormonal phases, across or within groups. A positive correlation of functional connectivity in the posterior part of the default mode network (DMN) was found with premenstrual-like symptoms in the hormonal contraceptives group. Using the current methodology, the studied resting state networks seem to show a decent stability throughout menstrual cycle phases. Also, no effect of hormonal contraceptive use is found. Interestingly, we show for the first time an association of DMN alterations with premenstrual-like symptoms, experienced during the inactive pill-phase by a sub-population of women.

Quality of life of people living with HIV/AIDS treated by the specialized service in Vitória-ES, Brazil / Qualidade de vida de pessoas que vivem com HIV/AIDS assistidas no serviço especializado em Vitória (ES), Brasil

The aim of this study is to establish the factors that influence the quality of life of people living with HIV/AIDS being treated at a specialized public service. The participants answered the questionnaire on sociodemographic conditions, issues related to HIV and daily habits. The quality of life was analyzed using the HIV/AIDS-targeted quality of life (HAT-QoL) instrument with 42 items divided into 9 fields: General Activity, Sexual Activity, Confidentiality Concerns, Health Concerns, Financial Concerns, HIV Awareness, Satisfaction with Life, Issues related to Medication and Trust in the Physician. Bivariate and multiple linear regressions were performed. Of the participants, 53.1% were women and had a mean age of 42 years. In analyzing the quality of life, the HAT-QoL domain with the lowest average was Financial Concerns (39.4), followed by Confidentiality Concerns (43.2), Sexual Activity (55.2) and Health Concerns (62. 88). There was an association between the variables: not being gainfully employed (p < 0.001), being mulatto or black (p = 0.045) and alcohol consumption (p = 0.041) with the worst quality of life scores. Inadequate socioeconomic and health conditions had a negative impact on the quality of life of people with HIV/AIDS.

O objetivo do presente estudo é verificar os fatores que influenciam na qualidade de vida das pessoas que vivem com HIV/AIDS assistidas no serviço especializado. Os entrevistados responderam os questionários sobre condições sociodemográficas, aspectos relacionados ao HIV e hábitos. A qualidade de vida foi analisada por meio do instrumento HAT-QoL, com 42 itens divididos em nove domínios: Atividade Geral, Atividade Sexual, Preocupações com Sigilo, Preocupação com a Saúde, Preocupação Financeira, Conscientização sobre o HIV, Satisfação com a Vida, Questões relativas à medicação e Confiança no médico. Análises bivariadas e regressão linear múltipla foram realizadas. Dos entrevistados, 53,1% eram mulheres e tinham média de idade de 42 anos. Na análise da qualidade de vida, o domínio do HAT-QoL com menor média foi Preocupação financeira (39,4), seguido de Preocupação com sigilo (43,2), Atividades sexuais (55,2) e Preocupação com a saúde (62,88). Houve associação entre as variáveis não ter vínculo trabalhista (p < 0,001), ser pardo ou negro (p = 0,045) e consumir bebida alcoólica (p = 0,041), com piores escores da qualidade de vida. Condições socioeconômicas e de saúde inadequadas apresentaram impacto negativo na qualidade de vida das pessoas com HIV/AIDS.

Functional Connectivity Changes and Executive and Social Problems in Neurofibromatosis Type I.

Neurofibromatosis type 1 (NF1) has regularly been associated with cognitive, social, and behavioral problems. The fact that many different cognitive and behavioral impairments have been observed in NF1 suggests that networks of brain regions are involved rather than specific brain regions. Here, we examined whether functional connectivity was different in NF1 and, if so, whether associations were present with cognitive, social, and behavioral outcomes. Fourteen NF1 patients (8 male, age: M=12.49, SD=2.65) and 30 healthy controls (HC; 23 male, age: M=12.30, SD=2.94; p=0.835) were included. Functional connectivity was assessed using functional resting-state scanning. We analyzed brain regions that have been associated with cognitive and social functions: the bilateral ventral anterior cingulate cortex (vACC), the bilateral amygdala, the bilateral orbitofrontal cortex (OFC), and the posterior cingulate cortex (PCC). For NF1 patients, connection strengths between brain regions showing HC-NF1 differences were correlated with parent reports of cognitive, social, and behavioral functioning. Compared to HC, patients showed differences in functional connectivity between the left vACC and the frontal cortex, insula, and subcortical areas (caudate, putamen), between the left amygdala and the frontal cortex, insula, supramarginal gyrus, and PCC/precuneus, and between the left OFC and frontal and subcortical areas (caudate, pallidum). In patients, indications were found for associations between increased frontofrontal and temporofrontal functional connectivity with cognitive, social, and behavioral deficits (r-range=0.536-0.851). NF1 patients showed differences in functional connectivity between areas associated with cognitive and social functioning when compared to controls. This, plus the fact that connectivity strengths in these networks were associated with worse cognitive, social, and behavioral outcomes, suggests a neuropathological basis for the widespread deficits observed in NF1.

Insula-Dorsal Anterior Cingulate Cortex Coupling is Associated with Enhanced Brain Reactivity to Smoking Cues.

The insula plays a critical role in maintaining nicotine dependence and reactivity to smoking cues. More broadly, the insula and the dorsal anterior cingulate cortex (dACC) are key nodes of the salience network (SN), which integrates internal and extrapersonal information to guide behavior. Thus, insula-dACC interactions may be integral in processing salient information such as smoking cues that facilitate continued nicotine use. We evaluated functional magnetic resonance imaging (fMRI) data from nicotine-dependent participants during rest, and again when they viewed smoking-related images. Greater insula-dACC coupling at rest was significantly correlated with enhanced smoking cue-reactivity in brain areas associated with attention and motor preparation, including the visual cortex, right ventral lateral prefrontal cortex, and the dorsal striatum. In an independent cohort, we found that insula-dACC connectivity was stable over 1-h delay and was not influenced by changes in subjective craving or expired carbon monoxide, suggesting that connectivity strength between these regions may be a trait associated with heightened cue-reactivity. Finally, we also showed that insula reactivity to smoking cues correlates with a rise in cue-reactivity throughout the entire SN, indicating that the insula's role in smoking cue-reactivity is not functionally independent, and may actually represent the engagement of the entire SN. Collectively, these data provide a more network-level understanding of the insula's role in nicotine dependence and shows a relationship between inherent brain organization and smoking cue-reactivity.

The Resting Brain of Alcoholics.

Chronic alcohol consumption affects multiple cognitive processes supported by far-reaching cerebral networks. To identify neurofunctional mechanisms underlying selective deficits, 27 sober alcoholics and 26 age-matched controls underwent resting-state functional magnetic resonance imaging and neuropsychological testing. Functional connectivity analysis assessed the default mode network (DMN); integrative executive control (EC), salience (SA), and attention (AT) networks; primary somatosensory, auditory, and visual (VI) input networks; and subcortical reward (RW) and emotion (EM) networks. The groups showed an extensive overlap of intrinsic connectivity in all brain networks examined, suggesting overall integrity of large-scale functional networks. Despite these similar patterns, connectivity analyses identified network-specific differences of weaker within-network connectivity and expanded connectivity to regions outside the main networks in alcoholics compared with controls. For AT and VI networks, better task performance was related to expanded connectivity in alcoholism, supporting the concept of network expansion as a neural mechanism for functional compensation. For default mode, SA, RW, and EC networks, both weaker within-network and expanded outside-network connectivity correlated with poorer performance and mood. Current smoking contributed to some of these abnormalities in connectivity. The observed pattern of resting-state connectivity might reflect neural vulnerability of intrinsic networking in alcoholics and suggests a mechanism to explain signature impairments in EM, RW evaluation, and EC ability.

Involuntary switching into the native language induced by electrocortical stimulation of the superior temporal gyrus: a multimodal mapping study.

We describe involuntary language switching from L2 to L1 evoked by electro-stimulation in the superior temporal gyrus in a 30-year-old right-handed Serbian (L1) speaker who was also a late Italian learner (L2). The patient underwent awake brain surgery. Stimulation of other portions of the exposed cortex did not cause language switching as did not stimulation of the left inferior frontal gyrus, where we evoked a speech arrest. Stimulation effects on language switching were selective, namely, interfered with counting behaviour but not with object naming. The coordinates of the positive site were combined with functional and fibre tracking (DTI) data. Results showed that the language switching site belonged to a significant fMRI cluster in the left superior temporal gyrus/supramarginal gyrus found activated for both L1 and L2, and for both the patient and controls, and did not overlap with the inferior fronto-occipital fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the superior longitudinal fasciculus (SLF). This area, also known as Stp, has a role in phonological processing. Language switching phenomenon we observed can be partly explained by transient dysfunction of the feed-forward control mechanism hypothesized by the DIVA (Directions Into Velocities of Articulators) model (Golfinopoulos, E., Tourville, J. A., & Guenther, F. H. (2010). The integration of large-scale neural network modeling and functional brain imaging in speech motor control.

Altered resting state connectivity of the insular cortex in individuals with fibromyalgia.

UNLABELLED: The insular cortex (IC) and cingulate cortex (CC) are critically involved in pain perception. Previously we demonstrated that fibromyalgia (FM) patients have greater connectivity between the insula and default mode network at rest, and that changes in the degree of this connectivity were associated with changes in the intensity of ongoing clinical pain. In this study we more thoroughly evaluated the degree of resting-state connectivity to multiple regions of the IC in individuals with FM and healthy controls. We also investigated the relationship between connectivity, experimental pain, and current clinical chronic pain. Functional connectivity was assessed using resting-state functional magnetic resonance imaging in 18 FM patients and 18 age- and sex-matched healthy controls using predefined seed regions in the anterior, middle, and posterior IC. FM patients exhibited greater connectivity between 1) right mid IC and right mid/posterior CC and right mid IC, 2) right posterior IC and left CC, and 3) right anterior IC and left superior temporal gyrus. Healthy controls displayed greater connectivity between left anterior IC and bilateral medial frontal gyrus/anterior cingulate cortex; and left posterior IC and right superior frontal gyrus. Within the FM group, greater connectivity between the IC and CC was associated with decreased pressure-pain thresholds. PERSPECTIVE: These data provide further support for altered resting-state connectivity between the IC and other brain regions known to participate in pain perception/modulation, which may play a pathogenic role in conditions such as FM. We speculate that altered IC connectivity is associated with the experience of chronic pain in individuals with FM.

Altered prefrontal connectivity after acute heroin administration during cognitive control.

Neuroimaging studies have reported reduced activity in a broad network of brain regions during response inhibition in heroin-dependent patients. However, how heroin in an acute dose modulates the neural correlates of response inhibition and the underlying brain connectivity has not yet been investigated. In this double-blind placebo-controlled study, we used functional magnetic resonance imaging to examine whether acute heroin administration changed whole brain activity during response inhibition in 26 heroin-dependent patients. We then applied dynamic causal modelling to investigate the effect of an acute dose of heroin on the functional interactions between the dorsal anterior cingulate cortex (dACC) and the bilateral inferior frontal gyri (IFG). Heroin acutely reduced dACC activity, as well as the inhibition-induced modulation of connectivity from the dACC to the right IFG compared with placebo. Furthermore, dACC activity was positively related to false alarm rates after placebo but not heroin administration. These results suggest that acute heroin administration impairs cognitive control in dependent patients by reducing the activity in the dACC activity and the functional connectivity from the dACC to the right IFG.

Altered functional connectivity of the default mode network in diffuse gliomas measured with pseudo-resting state fMRI.

The purpose of the current study was to explore whether brain tumors disrupt the integrity of the default mode network (DMN), a well-characterized resting-state fMRI network. We evaluated whether tumor grade, volume, post-surgical/clinical status, or location decreased the functional connectivity within the DMN in patients with gliomas. Task-based fMRI data was obtained from 68 diffuse glioma patients and 12 healthy volunteers. Pseudo-resting state fMRI data was calculated from task-based fMRI data using standard techniques. Data was preprocessed and DMN integrity was compared across WHO grade, tumor volume surgical status (new vs. recurrent tumors), age, and KPS using univariate and multivariate linear models. WHO grade was the most significant predictor of DMN integrity (P = 0.004), whereas T2 hyperintense lesion volume was not a predictor (P = 0.154). DMN integrity was lower in high-grade (WHO III­IV) compared with low-grade (WHO II) patients (P = 0.020). Tumors in the left parietal lobe showed a more impaired DMN compared with tumors in the frontal lobe, while tumors within and outside the network nodes did not differ significantly. Results suggest higher tumor grade along with prior surgery and/or treatment cause the largest reduction in DMN functional connectivity in patients with primary gliomas, and that tumor location has an impact on connectivity.

Increased power spectral density in resting-state pain-related brain networks in fibromyalgia.

Fibromyalgia (FM), characterized by chronic widespread pain, is known to be associated with heightened responses to painful stimuli and atypical resting-state functional connectivity among pain-related regions of the brain. Previous studies of FM using resting-state functional magnetic resonance imaging (rs-fMRI) have focused on intrinsic functional connectivity, which maps the spatial distribution of temporal correlations among spontaneous low-frequency fluctuation in functional MRI (fMRI) resting-state data. In the current study, using rs-fMRI data in the frequency domain, we investigated the possible alteration of power spectral density (PSD) of low-frequency fluctuation in brain regions associated with central pain processing in patients with FM. rsfMRI data were obtained from 19 patients with FM and 20 age-matched healthy female control subjects. For each subject, the PSDs for each brain region identified from functional connectivity maps were computed for the frequency band of 0.01 to 0.25 Hz. For each group, the average PSD was determined for each brain region and a 2-sample t test was performed to determine the difference in power between the 2 groups. According to the results, patients with FM exhibited significantly increased frequency power in the primary somatosensory cortex (S1), supplementary motor area (SMA), dorsolateral prefrontal cortex, and amygdala. In patients with FM, the increase in PSD did not show an association with depression or anxiety. Therefore, our findings of atypical increased frequency power during the resting state in pain-related brain regions may implicate the enhanced resting-state baseline neural activity in several brain regions associated with pain processing in FM.

Human brain functional network changes associated with enhanced and impaired attentional task performance.

How is the cognitive performance of the human brain related to its topological and spatial organization as a complex network embedded in anatomical space? To address this question, we used nicotine replacement and duration of attentionally demanding task performance (time-on-task), as experimental factors expected, respectively, to enhance and impair cognitive function. We measured resting-state fMRI data, performance and brain activation on a go/no-go task demanding sustained attention, and subjective fatigue in n = 18 healthy, briefly abstinent, cigarette smokers scanned repeatedly in a placebo-controlled, crossover design. We tested the main effects of drug (placebo vs Nicorette gum) and time-on-task on behavioral performance and brain functional network metrics measured in binary graphs of 477 regional nodes (efficiency, measure of integrative topology; clustering, a measure of segregated topology; and the Euclidean physical distance between connected nodes, a proxy marker of wiring cost). Nicotine enhanced attentional task performance behaviorally and increased efficiency, decreased clustering, and increased connection distance of brain networks. Greater behavioral benefits of nicotine were correlated with stronger drug effects on integrative and distributed network configuration and with greater frequency of cigarette smoking. Greater time-on-task had opposite effects: it impaired attentional accuracy, decreased efficiency, increased clustering, and decreased connection distance of networks. These results are consistent with hypothetical predictions that superior cognitive performance should be supported by more efficient, integrated (high capacity) brain network topology at greater connection distance (high cost). They also demonstrate that brain network analysis can provide novel and theoretically principled pharmacodynamic biomarkers of pro-cognitive drug effects in humans.

Default mode network functional connectivity altered in failed back surgery syndrome.

UNLABELLED: The purpose of this study was to identify alterations in the default mode network of failed back surgery syndrome patients as compared to healthy subjects. Resting state functional magnetic resonance imaging was conducted at 3 Tesla and data were analyzed with an independent component analysis. Results indicate an overall reduced functional connectivity of the default mode network and recruitment of additional pain modulation brain regions, including dorsolateral prefrontal cortex, insula, and additional sensory motor integration brain regions, including precentral and postcentral gyri, for failed back surgery syndrome patients. PERSPECTIVE: This article presents alterations in the default mode network of chronic low back pain patients with failed back surgery syndrome as compared to healthy participants.

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy.

PURPOSE: The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. METHODS: Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. KEY FINDINGS: Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. SIGNIFICANCE: Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE.

Brain imaging reveals that engagement of descending inhibitory pain pathways in healthy women in a low endogenous estradiol state varies with testosterone.

The combined oral contraceptive pill (COCP) has been implicated in the development of a number of chronic pain conditions. Modern COCP formulations produce a low endogenous estradiol, low progesterone environment similar to the early follicular phase of the natural menstrual cycle, with a variable effect on serum androgen levels. We used behavioural measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli in healthy women, in both a natural and COCP-induced low endogenous estradiol state, to investigate whether alterations in central pain processing may underlie these observations in COCP users. Although COCP users overall did not require lower temperatures to obtain a fixed pain intensity, alterations in the brain response to these stimuli were observed. In a subgroup of COCP users with significantly reduced serum testosterone, however, lower temperatures were required. Region-of-interest analysis revealed that within key regions of the descending pain inhibitory system, activity in response to noxious stimulation varied with serum testosterone levels in both groups of women. Of particular interest, in COCP users, activity in the rostral ventromedial medulla increased with increasing testosterone and in those women with low testosterone, was significantly reduced compared to controls. These findings suggest that, in a low endogenous estradiol state, testosterone may be a key factor in modulating pain sensitivity via descending pathways. Specifically, failure to engage descending inhibition at the level of the rostral ventromedial medulla may be responsible for the reduction in temperature required by COCP users with low circulating testosterone.

Transient crossed cerebellar diaschisis due to cerebral hyperperfusion following surgical revascularization for moyamoya disease: case report.

Crossed cerebellar diaschisis (CCD) often occurs after ischemic or hemorrhagic stroke that damages the cortico-ponto-cerebellar pathway. However, CCD due to cerebral hyperperfusion following cerebrovascular reconstruction is rare. A 61-year-old woman presented with transient CCD due to cerebral hyperperfusion following bypass surgery for adult moyamoya disease. She developed transient weakness of the right extremities and was diagnosed with moyamoya disease. First, she underwent superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis with indirect synangiosis on the left. Postoperative course was uneventful. Subsequently, she underwent STA-MCA anastomosis with indirect synangiosis on the right. She complained of mild headache on the right, and single photon emission computed tomography (SPECT) performed on the 7th postoperative day demonstrated hyperperfusion in the right frontal and temporal lobes associated with hypoperfusion in the left cerebellum. Magnetic resonance (MR) imaging demonstrated no new lesions and MR angiography showed patent STA-MCA bypass. Subsequent SPECT showed disappearance of both hyperperfusion and CCD. This case strongly suggests that cerebral hyperperfusion after bypass surgery for moyamoya disease may cause transient CCD. Although the clinical significance is still obscure, this phenomenon indicates the cortico-ponto-cerebellar pathway is interrupted due to hyperperfusion, suggesting the development of hyperperfusion syndrome. Careful observation of cerebral hemodynamics after bypass surgery is warranted to avoid hyperperfusion-related complications.

Effective connectivity of AKT1-mediated dopaminergic working memory networks and pharmacogenetics of anti-dopaminergic treatment.

Working memory is a limited capacity system that integrates and manipulates information across brief periods of time, engaging a network of prefrontal, parietal and subcortical brain regions. Genetic control of these heritable brain processes have been suggested by functional genetic variations influencing dopamine signalling, which affect prefrontal activity during complex working memory tasks. However, less is known about genetic control over component working memory cortical-subcortical networks in humans, and the pharmacogenetic implications of dopamine-related genes on cognition in patients receiving anti-dopaminergic drugs. Here, we examined predictions from basic models of dopaminergic signalling in cortical and cortical-subcortical circuitries implicated in dissociable working memory maintenance and manipulation processes. We also examined pharmacogenetic effects on cognition in the context of anti-dopaminergic drug therapy. Using dynamic causal models of functional magnetic resonance imaging in normal subjects (n = 46), we identified differentiated effects of functional polymorphisms in COMT, DRD2 and AKT1 genes on prefrontal-parietal and prefrontal-striatal circuits engaged during maintenance and manipulation, respectively. Cortical synaptic dopamine monitored by the COMT Val158Met polymorphism influenced prefrontal control of both parietal processing in working memory maintenance and striatal processing in working memory manipulation. DRD2 and AKT1 polymorphisms implicated in DRD2 signalling influenced only the prefrontal-striatal network associated with manipulation. In the context of anti-psychotic drugs, the DRD2 and AKT1 polymorphisms altered dose-response effects of anti-psychotic drugs on cognition in schizophrenia (n = 111). Thus, we suggest that genetic modulation of DRD2-AKT1-related prefrontal-subcortical circuits could at least in part influence cognitive dysfunction in psychosis and its treatment.

Motor deficits correlate with resting state motor network connectivity in patients with brain tumours.

While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery.

Dysfunctional connectivity patterns in chronic heroin users: an fMRI study.

Recent functional neuroimaging studies have examined cognitive inhibitory control, decision-making and stress regulation in heroin addiction using a cue-reactivity paradigm. Few studies have considered impairments in heroin users from an integrated perspective for evaluation of their brain functions. We hypothesized that the brain regions that are dysregulated in the chronic heroin users during cue-reactivity studies may also show dysfunctional connectivity in memory, inhibition and motivation-related dysfunctions during a resting state free of cues. The present study used resting functional magnetic resonance imaging (fMRI) to compare the interaction of brain regions between 12 chronic heroin users and 12 controls by employing a novel graph theory analysis (GTA) method. As a data-driven approach, GTA has the advantage of evaluating the strength as well as the temporal and spatial patterns of interactions among the brain regions. Abnormal topological properties were explored in the brain of chronic heroin users, such as the dysfunctional connectivity in the prefrontal cortex, ACC, SMA, ventral striatum, insula, amygdala and hippocampus. Our results suggest that GTA is a useful tool in defining dysregulated neural networks even during rest. This dysfunctional brain connectivity may contribute to decrease self-control, impaired inhibitory function as well deficits in stress regulation in chronic heroin users.

Reading impairment in a patient with missing arcuate fasciculus.

We describe the case of a child ("S") who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor-orientation directions in S's brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor-orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts.