Increased grey matter volume and associated resting-state functional connectivity in chronic spontaneous urticaria: A structural and functional MRI study

Background and purposeChronic itch is one of the most common irritating sensations, yet its mechanisms have not been fully elucidated. Although some studies have revealed relationships between itching and brain function, the structural changes in the brain induced by chronic itching, such as those accompanying chronic spontaneous urticaria (CSU), remain unclear. In this study, we aimed to explore the potential changes in brain structure and the associated functional circuitry in CSU patients to generate insights to aid chronic itch management.MethodsForty CSU patients and forty healthy controls (HCs) were recruited. Seven-day urticaria activity score (UAS7) values were collected to evaluate clinical symptoms. Voxel-based morphometry (VBM) and seed-based resting-state functional connectivity (rs-FC) analysis were used to assess structural changes in the brain and associated changes in functional circuitry.ResultsCompared with HCs, CSU patients had significantly increased grey matter (GM) volume in the right premotor cortex, left fusiform cortex, and cerebellum. UAS7 values were positively associated with GM volume in the left fusiform cortex. In CSU patients relative to HCs, the left fusiform cortex as extracted by VBM analysis demonstrated decreased functional connectivity with the right orbitofrontal cortex, medial prefrontal cortex (mPFC), premotor cortex, primary motor cortex (MI), and cerebellum and increased functional connectivity with the right posterior insular cortex, primary somatosensory cortex (SI), and secondary somatosensory cortex (SII). The left cerebellum as extracted from VBM analysis demonstrated decreased functional connectivity with the right supplementary motor area (SMA) and MI in CSU patients relative to HCs.ConclusionsOur findings indicate that patients suffering from chronic itching conditions, such as CSU, are likely to demonstrate altered GM volume in some brain regions. These changes may affect not only the sensorimotor area but also brain regions associated with cognitive function.     

Retrosplenial cortex connectivity in schizophrenia

In this paper, we build on our previous analysis [Bluhm, R.L., Miller, J., Lanius, R.A., Osuch, E.A., Boksman, K., Neufeld, R.W.J., et al., 2007 Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophrenia Bulletin 33, 1004–1012] of resting state connectivity in schizophrenia by examining alterations in connectivity of the retrosplenial cortex. We have previously demonstrated altered connectivity of the posterior cingulate/precuneus, particularly with other regions of the “default network” (which includes the medial prefrontal cortex and bilateral lateral parietal cortex). It was hypothesized that the retrosplenial cortex would show aberrant patterns of connectivity with regions of the default network and regions associated with memory. Patients with schizophrenia (N = 17) and healthy controls (N = 17) underwent a 5.5-min resting functional magnetic resonance imaging scan. Lower correlations were observed in patients with schizophrenia than in healthy controls between the retrosplenial cortex and both the temporal lobe and regions of the default network. In patients with schizophrenia, activity in the retrosplenial cortex correlated negatively with activity in bilateral anterior cingulate gyrus/medial prefrontal cortex (BA 32/10), despite the fact that these regions, as part of the default network, were expected to show positive correlations in activity. Connectivity of the retrosplenial cortex was greater in patients with more positive symptoms with areas previously associated with hallucinations, particularly the left superior temporal gyrus. These results suggest that spontaneous activity in the retrosplenial cortex during rest is altered in patients with schizophrenia. These alterations may help to explain alterations in self-oriented processing in this patient population.     

Mapping Different Intra-Hemispheric Parietal-Motor Networks Using Twin Coil TMS

BackgroundAccumulating evidence suggests anatomical and functional differences in connectivity between the anterior and posterior parts of the inferior-parietal lobule (IPL) and the frontal motor areas.Objective/HypothesisThis study investigates whether different intra-hemispheric parietal-motor interactions can be observed along the anterior–posterior axis of the IPL in the resting human brain.MethodsWe use a twin coil transcranial magnetic stimulation technique to test intra-hemispheric interactions between three points adjacent to the intra-parietal sulcus (anterior, central, posterior) and the ipsilateral primary motor cortex (M1) at rest in both hemispheres.ResultsWe found that stimulation of the anterior IPL resulted in an inhibition of the ipsilateral M1 in both hemispheres. Stimulation of the central and posterior IPL resulted in a facilitatory effect on ipsilateral M1 in the left but not for the right hemisphere. Additionally we show that there is considerable inter-subject variability concerning the optimal parietal facilitatory and inhibitory position.ConclusionsThe IPL has distinct inhibitory and facilitatory connections to the ipsilateral M1. Whereas inhibitory connections are observed in both hemispheres, facilitatory connections are asymmetric. These parietal-motor networks may represent the basis for the functional differences between these regions in reaching and grasping tasks and mirror the functional asymmetry observed in the motor system. From a practical point of view, we note that the inter-subject variability means that future TMS studies of the parietal area might consider a hot-spot localization similar to the procedures commonly used for M1.     

Pathophysiology of unilateral asterixis due to thalamic lesion

ObjectiveUnilateral asterixis has been reported in patients with thalamic lesion. This study aims at elucidating the pathophysiology of the thalamic asterixis.MethodsTwo cases with unilateral asterixis caused by an infarction in the lateral thalamus were studied by analysing the asterixis-related cortical activities, transcranial magnetic stimulation (TMS) for motor cortex excitability and probabilistic diffusion tractography for the thalamo-cortical connectivity.ResultsAveraging of electroencephalogram (EEG) time-locked to the asterixis revealed rhythmic oscillations of a beta band at the central area contralateral to the affected hand. TMS revealed a decrease in the motor evoked potential (MEP) amplitude and a prolongation of the silent period (SP). The anatomical mapping of connections between the thalamus and cortical areas using a diffusion-weighted image (DWI) showed that the lateral thalamus involved by the infarction was connected to the premotor cortex, the primary motor cortex (M1) and the primary somatosensory cortex (S1) of the corresponding hemisphere.ConclusionsThe thalamic asterixis is mediated by the sensorimotor cortex, which is subjected to excessive inhibition as a result of the thalamic lesion involving the ventral lateral nucleus.SignificanceThis is the first demonstration of participation of the sensorimotor cortex in the generation of asterixis due to the lateral thalamic lesion.     

Task-specific interhemispheric hypoconnectivity in writer’s cramp – An EEG study

ObjectiveWriter’s cramp (WC) is a focal task-specific dystonia characterized by abnormal posturing of the hand muscles during handwriting, but not during other tasks that involve the same set of muscles and objects such as sharpening a pencil. Our objective was to investigate the pathophysiology underlying the task specificity of this disorder using EEG. We hypothesized that premotor-parietal connectivity will be lower in WC patients specifically during handwriting and motor imagery of handwriting.MethodsWe recruited 15 WC patients and 15 healthy controls. EEG was recorded while participants performed 4 tasks – writing with a pencil, sharpening a pencil, imagining writing and imagining sharpening. We determined the connectivity changes between relevant brain regions during these tasks.ResultsWe found reduced interhemispheric alpha coherence in the sensorimotor areas in WC patients exclusively during handwriting. WC patients also showed less reduction of task-related beta spectral power and a trend for reduced premotor-parietal coherence during motor tasks.ConclusionWe could not confirm an abnormality in premotor-parietal connectivity specific to handwriting by this method. However, there was a task-specific reduction in interhemispheric alpha connectivity in WC patients, whose behavioral correlate remains unknown.SignificanceInterhemispheric alpha connectivity can be a potential interventional target in WC.     

Cortico-cortical connectivity between the superior and inferior parietal lobules and the motor cortex assessed by intraoperative dual cortical stimulation

BackgroundThe function of the primate’s posterior parietal cortex (PPC) in sensorimotor transformations is well-established, though in humans its complexity is still challenging. Well-established models indicate that the posterior parietal cortex influences motor output indirectly, by means of connections to the premotor cortex, which in turn is directly connected to the motor cortex.ObjectiveThe possibility that the PPC could be at the origin of direct afferents to M1 has been suggested in humans but has never been confirmed directly. We aim to do so in the present study by using the novel technique of paired intraoperative cortical stimulation.MethodsIn the present cross-sectional study, we assessed during intraoperative monitoring of the corticospinal tract in brain tumour patients the existence of short-latency effects of parietal stimulation on corticospinal excitability to the upper limb. MEPs were evoked by test stimuli over the motor cortex, which were preceded in some trials by conditioning stimuli on the PPC.ResultsWe identified two active cortical loci. One in the inferior parietal lobule exerted short-latency excitatory effects and one in the superior parietal lobule that drove short-latency inhibitory effects on cortical motor output. All active foci were distributed in the rostral portion of the PPC and on the postcentral sulcus.ConclusionsFor the first time in humans, the present data show direct evidence in favour of a distributed system of connections from the posterior parietal cortex to the ipsilateral primary motor cortex. In addition, we show that dual cortical stimulation is a novel and efficient technique to investigate intraoperative brain connectivity in the anaesthetized patient.     

Neural noise and cortical inhibition in schizophrenia

BackgroundNeural information processing is subject to noise and this leads to variability in neural firing and behavior. Schizophrenia has been associated with both more variable motor control and impaired cortical inhibition, which is crucial for excitatory/inhibitory balance in neural commands.HypothesisIn this study, we hypothesized that impaired intracortical inhibition in motor cortex would contribute to task-related motor noise in schizophrenia.MethodsWe measured variability of force and of electromyographic (EMG) activity in upper limb and hand muscles during a visuomotor grip force-tracking paradigm in patients with schizophrenia (N = 25), in unaffected siblings (N = 17) and in healthy control participants (N = 25). Task-dependent primary motor cortex (M1) excitability and inhibition were assessed using transcranial magnetic stimulation (TMS).ResultsDuring force maintenance patients with schizophrenia showed increased variability in force and EMG, despite similar mean force and EMG magnitudes. Compared to healthy controls, patients with schizophrenia also showed increased M1 excitability and reduced cortical inhibition during grip-force tracking. EMG variability and force variability correlated negatively to cortical inhibition in patients with schizophrenia. EMG variability also correlated positively to negative symptoms. Siblings had similar variability and cortical inhibition compared to controls. Increased EMG and force variability indicate enhanced motor noise in schizophrenia, which relates to reduced motor cortex inhibition.ConclusionThe findings suggest that excessive motor noise in schizophrenia may arise from an imbalance of M1 excitation/inhibition of GABAergic origin. Thus, higher motor noise may provide a useful marker of impaired cortical inhibition in schizophrenia.     

Abnormal Causal Connectivity by Structural Deficits in First-Episode,Drug-Naive Schizophrenia at Rest

Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.Key words: first-episode schizophrenia, causal effect, structural deficits, voxel-based morphometry, Granger causality analysis     

Motor imagery evokes strengthened activation in sensorimotor areas and its effective connectivity related to cognitive regions in patients with complete spinal cord injury

The objective of this study was to investigate the alterations of brain activation and effective connectivity during motor imagery (MI) in complete spinal cord injury (CSCI) patients and to reveal a potential mechanism of MI in motor rehabilitation of CSCI patients. Fifteen CSCI patients and twenty healthy controls underwent the MI task-related fMRI scan, and the motor execution (ME) task only for healthy controls. The brain activation patterns of the two groups during MI, and CSCI patients during the MI task and healthy controls during the ME task were compared. Then the significantly changed brain activation areas in CSCI patients during the MI task were used as regions of interest for effective connectivity analysis, using a voxel-wise granger causality analysis (GCA) method. Compared with healthy controls, increased activations in left primary sensorimotor cortex and bilateral cerebellar lobules IV-VI were detected in CSCI patients during the MI task, and the activation level of these areas even equaled that of healthy controls during the ME task. Furthermore, GCA revealed decreased effective connectivity from sensorimotor related areas (primary sensorimotor cortex and cerebellar lobules IV-VI) to cognitive related areas (prefrontal cortex, precuneus, middle temporal gyrus, and inferior temporal gyrus) in CSCI patients. Our findings demonstrated that motor related brain areas can be functionally preserved and activated through MI after CSCI, it maybe the potential mechanism of MI in the motor rehabilitation of CSCI patients. In addition, Sensorimotor related brain regions have less influence on the cognitive related regions in CSCI patients during MI (The trial registration number: ChiCTR2000032793).

     

Changes in Default-Mode Network Associated With Childhood Trauma in Schizophrenia

BackgroundThere is considerable evidence of dysconnectivity within the default-mode network (DMN) in schizophrenia, as measured during resting-state functional MRI (rs-fMRI). History of childhood trauma (CT) is observed at a higher frequency in schizophrenia than in the general population, but its relationship to DMN functional connectivity has yet to be investigated.MethodsCT history and rs-fMRI data were collected in 65 individuals with schizophrenia and 132 healthy controls. Seed-based functional connectivity between each of 4 a priori defined seeds of the DMN (medial prefrontal cortex, right and left lateral parietal lobes, and the posterior cingulate cortex) and all other voxels of the brain were compared across groups. Effects of CT on functional connectivity were examined using multiple regression analyses. Where significant associations were observed, regression analyses were further used to determine whether variance in behavioral measures of Theory of Mind (ToM), previously associated with DMN recruitment, were explained by these associations.ResultsSeed-based analyses revealed evidence of widespread reductions in functional connectivity in patients vs controls, including between the left/right parietal lobe (LP) and multiple other regions, including the parietal operculum bilaterally. Across all subjects, increased CT scores were associated with reduced prefrontal-parietal connectivity and, in patients, with increased prefrontal-cerebellar connectivity also. These CT-associated differences in DMN connectivity also predicted variation in behavioral measures of ToM.ConclusionsThese findings suggest that CT history is associated with variation in DMN connectivity during rs-fMRI in patients with schizophrenia and healthy participants, which may partly mediate associations observed between early life adversity and cognitive performance.     

Transcranial direct current stimulation facilitates response inhibition through dynamic modulation of the fronto-basal ganglia network

BackgroundResponse inhibition refers to the ability to stop an on-going action quickly when it is no longer appropriate. Previous studies showed that transcranial direct current stimulation (tDCS) applied with the anode over the right inferior frontal cortex (rIFC), a critical node of the fronto-basal ganglia inhibitory network, improved response inhibition. However, the tDCS effects on brain activity and network connectivity underlying this behavioral improvement are not known.ObjectiveThis study aimed to address the effects of tDCS applied with the anode over the rIFC on brain activity and network functional connectivity underlying the behavioral change in response inhibition.MethodsThirty participants performed a stop-signal task in a typical laboratory setting as a baseline during the first study visit (i.e., Session 1). In the second visit (at least 24 h after Session 1), all participants underwent resting-state functional magnetic resonance imaging (rsfMRI) scans before and after 1.5 mA tDCS (Anodal or Sham). Immediately following the post-tDCS rsfMRI, participants performed the same stop-signal task as in Session 1 during an event-related fMRI (efMRI) scan in a 3T scanner. Changes in task performance, i.e., the stop-signal response time (SSRT), a measure of response inhibition efficiency, was determined relative to the participants’ own baseline performance in Session 1.ResultsConsistent with previous findings, Anodal tDCS facilitated the SSRT. efMRI results showed that Anodal tDCS strengthened the functional connectivity between right pre-supplementary motor area (rPreSMA) and subthalamic nuclei during Stop responses. rsfMRI revealed changes in intrinsic connectivity between rIFC and caudate, and between rIFC, rPreSMA, right inferior parietal cortex (rIPC), and right dorsolateral prefrontal cortex (rDLPFC) after Anodal tDCS. In addition, corresponding to the regions of rsfMRI connectivity change, the efMRI BOLD signal in the rDLPFC and rIPC during Go responses accounted for 74% of the variance in SSRT after anodal tDCS, indicating an effect of tDCS on the Go-Stop process.ConclusionThese results indicate that tDCS with the anode over the rIFC facilitates response inhibition by modulating neural activity and functional connectivity in the fronto-basal ganglia as well as rDLPFC and rIPC as an integral part of the response inhibition network.     

Cerebellar–cortical dysconnectivity in resting‐state associated with sensorimotor tasks in schizophrenia

Abnormalities of cerebellar function have been implicated in the pathophysiology of schizophrenia. Since the cerebellum has afferent and efferent projections to diverse brain regions, abnormalities in cerebellar lobules could affect functional connectivity with multiple functional systems in the brain. Prior studies, however, have not examined the relationship of individual cerebellar lobules with motor and nonmotor resting‐state functional networks. We evaluated these relationships using resting‐state fMRI in 30 patients with a schizophrenia‐spectrum disorder and 37 healthy comparison participants. For connectivity analyses, the cerebellum was parcellated into 18 lobular and vermal regions, and functional connectivity of each lobule to 10 major functional networks in the cerebrum was evaluated. The relationship between functional connectivity measures and behavioral performance on sensorimotor tasks (i.e., finger‐tapping and postural sway) was also examined. We found cerebellar–cortical hyperconnectivity in schizophrenia, which was predominantly associated with Crus I, Crus II, lobule IX, and lobule X. Specifically, abnormal cerebellar connectivity was found to the cerebral ventral attention, motor, and auditory networks. This cerebellar–cortical connectivity in the resting‐state was differentially associated with sensorimotor task‐based behavioral measures in schizophrenia and healthy comparison participants—that is, dissociation with motor network and association with nonmotor network in schizophrenia. These findings suggest that functional association between individual cerebellar lobules and the ventral attentional, motor, and auditory networks is particularly affected in schizophrenia. They are also consistent with dysconnectivity models of schizophrenia suggesting cerebellar contributions to a broad range of sensorimotor and cognitive operations.     

Neural correlates of motor recovery after robot-assisted stroke rehabilitation: a case series study

ABSTRACT

Robot-assisted bilateral arm therapy (RBAT) has shown promising results in stroke rehabilitation; however, connectivity mapping of the sensorimotor networks after RBAT remains unclear. We used fMRI before and after RBAT and a dose-matched control intervention (DMCI) to explore the connectivity changes in 6 subacute stroke patients. Sensorimotor functions improved in the RBAT and DMCI groups after treatment. Enhanced activation changes were observed in bilateral primary motor cortex (M1) and bilateral supplementary motor area (SMA) after RBAT. Dynamic causal model analysis revealed that interhemispheric connections were enhanced in RBAT patients. These preliminary findings suggest that intracortical and intercortical coupling might underlie poststroke RBAT.     

Parieto-motor Cortical Dysfunction in Primary Cervical Dystonia

BackgroundDystonia is considered as a motor network disorder involving the dysfunction of the posterior parietal cortex, a region involved in preparing and executing reaching movements.Objective/hypothesisWe used transcranial magnetic stimulation to test the hypothesis that cervical dystonic patients may have a disrupted parieto-motor connectivity.MethodsWe enrolled 14 patients with primary cervical dystonia and 14 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area. Changes in the amplitudes of motor evoked potential were analyzed as an index of parieto-motor effective connectivity. Patients and healthy subjects were also evaluated with a reaching task. Reaction and movement times were measured.ResultsIn healthy subjects, but not in dystonic patients, there was a facilitation of motor evoked potential amplitudes when the conditioning parietal stimulus preceded the test stimulus applied over the primary motor area by 4 ms. Reaction and movement times were significantly slower in patients than in controls. In dystonic patients, the relative strength of parieto-motor connectivity correlated with movement times.ConclusionsParieto-motor cortical connectivity is impaired in cervical dystonic patients. This neurophysiological trait is associated with slower reaching movements.     

Mapping intrinsic functional brain changes and repetitive transcranial magnetic stimulation neuromodulation in idiopathic restless legs syndrome: a resting-state functional magnetic resonance imaging study

ObjectiveThe objectives of this study were, first, to explore differences in brain activity between normal people and idiopathic restless legs syndrome (RLS) patients during asymptomatic periods; and, second, to determine whether administering repetitive transcranial magnetic stimulation (rTMS) to specific cortical regions would reverse any observed differences in brain activity and alleviate patient symptoms.MethodsFifteen idiopathic RLS patients (nine drug-naive patients) and 14 gender- and age-matched healthy controls were enrolled. Resting-state functional magnetic resonance imaging was used to measure the amplitude of low-frequency fluctuations (ALFF) in spontaneous brain activity during asymptomatic periods. Seven patients received high-frequency (5 Hz) rTMS directed toward the leg area of the primary motor cortex. Scores on the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale and ALFF values were measured before and after treatment.ResultsCompared with healthy controls, RLS patients showed lower ALFF in the sensorimotor and visual processing regions, and higher ALFF in the insula, parahippocampal and hippocampal gyri, left posterior parietal areas, and brainstem. These results were largely conserved when only drug-naive patients were considered. After rTMS treatment, ALFF in several sensorimotor and visual regions were significantly elevated and IRLSSG Rating Scale scores decreased, indicating improved RLS symptoms.ConclusionsHigh-frequency rTMS delivered to the leg area of the primary motor cortex may raise functional activity in the sensorimotor and occipital regions, leading to improve symptoms in RLS patients. These results provide novel insight into RLS pathophysiology and suggest a potential mechanism for rTMS therapy in idiopathic RLS patients.     

Altered sensorimotor integration in multiple sclerosis: A combined neurophysiological and functional MRI study

ObjectiveTo explore whether abnormal thalamic resting-state functional connectivity (rsFC) contributes to altered sensorimotor integration and hand dexterity impairment in multiple sclerosis (MS).MethodsTo evaluate sensorimotor integration, we recorded kinematic features of index finger abductions during somatosensory temporal discrimination threshold (STDT) testing in 36 patients with relapsing-remitting MS and 39 healthy controls (HC). Participants underwent a multimodal 3T structural and functional MRI protocol.ResultsPatients had lower index finger abduction velocity during STDT testing compared to HC. Thalamic rsFC with the precentral and postcentral gyri, supplementary motor area (SMA), insula, and basal ganglia was higher in patients than HC. Intrathalamic rsFC and thalamic rsFC with caudate and insula bilaterally was lower in patients than HC. Finger movement velocity positively correlated with intrathalamic rsFC and negatively correlated with thalamic rsFC with the precentral and postcentral gyri, SMA, and putamen.ConclusionsAbnormal thalamic rsFC is a possible substrate for altered sensorimotor integration in MS, with high intrathalamic rsFC facilitating finger movements and increased thalamic rsFC with the basal ganglia and sensorimotor cortex contributing to motor performance deterioration.SignificanceThe combined study of thalamic functional connectivity and upper limb sensorimotor integration may be useful in identifying patients who can benefit from early rehabilitation to prevent upper limb motor impairment.     

Frontostriatal activity and connectivity increase during proactive inhibition across adolescence and early adulthood

During adolescence, functional and structural changes in the brain facilitate the transition from childhood to adulthood. Because the cortex and the striatum mature at different rates, temporary imbalances in the frontostriatal network occur. Here, we investigate the development of the subcortical and cortical components of the frontostriatal network from early adolescence to early adulthood in 60 subjects in a cross‐sectional design, using functional MRI and a stop‐signal task measuring two forms of inhibitory control: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping). During development, reactive inhibition improved: older subjects were faster in reactive inhibition. In the brain, this was paralleled by an increase in motor cortex suppression. The level of proactive inhibition increased, with older subjects slowing down responding more than younger subjects when anticipating a stop‐signal. Activation increased in the right striatum, right ventral and dorsal inferior frontal gyrus, and supplementary motor area. Moreover, functional connectivity during proactive inhibition increased between striatum and frontal regions with age. In conclusion, we demonstrate that developmental improvements in proactive inhibition are paralleled by increases in activation and functional connectivity of the frontostriatal network. These data serve as a stepping stone to investigate abnormal development of the frontostriatal network in disorders such as schizophrenia and attention‐deficit hyperactivity disorder. Hum Brain Mapp 35:4415–4427, 2014. © 2014 Wiley Periodicals, Inc .     

Subcortical motor plasticity in patients with sporadic ALS: An fMRI study

OBJECTIVE: To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. METHODS: We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. RESULTS: Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. CONCLUSIONS: Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction.     

Schizophrenic Patients and Their Unaffected Siblings Share Increased Resting-State Connectivity in the Task-Negative Network but Not Its Anticorrelated Task-Positive Network

Background:

Abnormal connectivity of the anticorrelated intrinsic networks, the task-negative network (TNN), and the task-positive network (TPN) is implicated in schizophrenia. Comparisons between schizophrenic patients and their unaffected siblings enable further understanding of illness susceptibility and pathophysiology. We examined the resting-state connectivity differences in the intrinsic networks between schizophrenic patients, their unaffected siblings, and healthy controls.

Methods:

Resting-state functional magnetic resonance images were obtained from 25 individuals in each subject group. The posterior cingulate cortex/precuneus and right dorsolateral prefrontal cortex were used as seed regions to identify the TNN and TPN through functional connectivity analysis. Interregional connectivity strengths were analyzed using overlapped intrinsic networks composed of regions common to all subject groups.

Results:

Schizophrenic patients and their unaffected siblings showed increased connectivity in the TNN between the bilateral inferior temporal gyri. By contrast, schizophrenic patients alone demonstrated increased connectivity between the posterior cingulate cortex/precuneus and left inferior temporal gyrus and between the ventral medial prefrontal cortex and right lateral parietal cortex in the TNN. Schizophrenic patients exhibited increased connectivity between the left dorsolateral prefrontal cortex and right inferior frontal gyrus in the TPN relative to their unaffected siblings, though this trend only approached statistical significance in comparison to healthy controls.

Conclusion:

Resting-state hyperconnectivity of the intrinsic networks may disrupt network coordination and thereby contribute to the pathophysiology of schizophrenia. Similar, though milder, hyperconnectivity of the TNN in unaffected siblings of schizophrenic patients may contribute to the identification of schizophrenia endophenotypes and ultimately to the determination of schizophrenia risk genes.     

Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment

BackgroundBrain imaging studies of early Alzheimer's disease (AD) have shown decreased metabolism predominantly in the posterior cingulate cortex (PCC), medial temporal lobe, and inferior parietal lobe. This study investigated functional connectivity between these regions, as well as connectivity between these regions and the whole brain.MethodsFunctional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies were performed in subjects with early AD, mild cognitive impairment (MCI), and normal controls.ResultsThe data indicate both decreased fiber connections and disrupted connectivity between the hippocampus and PCC in early AD. The MCI group showed reduced fiber numbers derived from PCC and hippocampus to the whole brain.ConclusionsThe fMRI and DTI results confirmed decreased connectivity from both the PCC and hippocampus to the whole brain in MCI and AD and reduction in connectivity between these two regions, which plausibly represents an early imaging biomarker for AD.