Subcortical electrostimulation to identify network subserving motor control.

PubMed

Schucht, Philippe; Moritz-Gasser, Sylvie; Herbet, Guillaume; Raabe, Andreas; Duffau, Hugues

2013-11-01

Recent anatomical-functional studies have transformed our understanding of cerebral motor control away from a hierarchical structure and toward parallel and interconnected specialized circuits. Subcortical electrical stimulation during awake surgery provides a unique opportunity to identify white matter tracts involved in motor control. For the first time, this study reports the findings on motor modulatory responses evoked by subcortical stimulation and investigates the cortico-subcortical connectivity of cerebral motor control. Twenty-one selected patients were operated while awake for frontal, insular, and parietal diffuse low-grade gliomas. Subcortical electrostimulation mapping was used to search for interference with voluntary movements. The corresponding stimulation sites were localized on brain schemas using the anterior and posterior commissures method. Subcortical negative motor responses were evoked in 20/21 patients, whereas acceleration of voluntary movements and positive motor responses were observed in three and five patients, respectively. The majority of the stimulation sites were detected rostral of the corticospinal tract near the vertical anterior-commissural line, and additional sites were seen in the frontal and parietal white matter. The diverse interferences with motor function resulting in inhibition and acceleration imply a modulatory influence of the detected fiber network. The subcortical stimulation sites were distributed veil-like, anterior to the primary motor fibers, suggesting descending pathways originating from premotor areas known for negative motor response characteristics. Further stimulation sites in the parietal white matter as well as in the anterior arm of the internal capsule indicate a large-scale fronto-parietal motor control network. Copyright © 2012 Wiley Periodicals, Inc.

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia.

PubMed

Komatsu, Takayuki; Nomura, Tomohisa; Takami, Hiroki; Sakamoto, So; Mizuno, Keiko; Sekii, Hajime; Hatta, Kotaro; Sugita, Manabu

A 42-year-old Japanese woman with a 10-year history of schizophrenia was admitted due to a disturbance in consciousness that met the diagnostic criteria for both neuroleptic malignant syndrome (NMS) and malignant catatonia. Despite systemic supportive treatments, the catatonic symptoms preceding autonomic symptoms persisted. The symptoms improved after lorazepam administration, leading to a retrospective diagnosis of malignant catatonia. Catatonia is thought to be caused by a dysfunction of ganmma-aminobutyric acid type A receptors in the cortico-cortical networks of the frontal lobes, which causes hypoactivity of the dopaminergic transmission in the subcortical areas. Identifying the catatonic symptoms preceding autonomic symptoms could aid in distinguishing malignant catatonia from NMS.

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia

PubMed Central

Komatsu, Takayuki; Nomura, Tomohisa; Takami, Hiroki; Sakamoto, So; Mizuno, Keiko; Sekii, Hajime; Hatta, Kotaro; Sugita, Manabu

2016-01-01

A 42-year-old Japanese woman with a 10-year history of schizophrenia was admitted due to a disturbance in consciousness that met the diagnostic criteria for both neuroleptic malignant syndrome (NMS) and malignant catatonia. Despite systemic supportive treatments, the catatonic symptoms preceding autonomic symptoms persisted. The symptoms improved after lorazepam administration, leading to a retrospective diagnosis of malignant catatonia. Catatonia is thought to be caused by a dysfunction of ganmma-aminobutyric acid type A receptors in the cortico-cortical networks of the frontal lobes, which causes hypoactivity of the dopaminergic transmission in the subcortical areas. Identifying the catatonic symptoms preceding autonomic symptoms could aid in distinguishing malignant catatonia from NMS. PMID:27725556

High definition-transcranial direct current stimulation changes older adults' subjective sleep and corresponding resting-state functional connectivity.

PubMed

Sheng, Jing; Xie, Chao; Fan, Dong-Qiong; Lei, Xu; Yu, Jing

2018-07-01

With advanced age, older adults show functional deterioration in sleep. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation, modulates individuals' behavioral performance in various cognitive domains. However, the modulation effect and neural mechanisms of tDCS on sleep, especially for the elderly population are not clear. Here, we aimed to investigate whether high-definition transcranial direct current stimulation (HD-tDCS) could modulate community-dwelling older adults' subjective sleep and whether these potential improvements are associated with the large-scale brain activity alterations recorded by functional magnetic resonance imaging. Thirty-one older adults were randomly allocated to the HD-tDCS group and the control group. HD-tDCS was applied for 25 min at 1.5 mA per day for two weeks. The anode electrode was placed over the left dorsolateral prefrontal cortex, surrounded by 4 cathodes at 7 cm radius. All participants completed sleep neuropsychological assessments and fMRI scans individually before and after intervention. Behaviorally, we observed a HD-tDCS-induced enhancement of older adults' sleep duration. On the aspect of the corresponding neural alterations, we observed that HD-tDCS decreased the functional connectivity between the default mode network (DMN) and subcortical network. More importantly, the decoupling connectivity of the DMN-subcortical network was correlated with the improvements of subjective sleep in the HD-tDCS group. Our findings add novel behavioral and neural evidences about tDCS-induced sleep improvement in community-dwelling older adults. With further development, tDCS may be used as an alternative treatment for sleep disorders and alleviate the dysfunction of brain networks induced by aging. Copyright © 2018 Elsevier B.V. All rights reserved.

Face processing in autism spectrum disorders: from brain regions to brain networks

PubMed Central

Nomi, Jason S.; Uddin, Lucina Q.

2015-01-01

Autism spectrum disorder (ASD) is characterized by reduced attention to social stimuli including the human face. This hypo-responsiveness to stimuli that are engaging to typically developing individuals may result from dysfunctioning motivation, reward, and attention systems in the brain. Here we review an emerging neuroimaging literature that emphasizes a shift from focusing on hypo-activation of isolated brain regions such as the fusiform gyrus, amygdala, and superior temporal sulcus in ASD to a more holistic approach to understanding face perception as a process supported by distributed cortical and subcortical brain networks. We summarize evidence for atypical activation patterns within brain networks that may contribute to social deficits characteristic of the disorder. We conclude by pointing to gaps in the literature and future directions that will continue to shed light on aspects of face processing in autism that are still under-examined. In particular, we highlight the need for more developmental studies and studies examining ecologically valid and naturalistic social stimuli. PMID:25829246

Dopamine homeostasis: brain functional connectivity in reward deficiency syndrome.

PubMed

Febo, Marcelo; Blum, Kenneth; Badgaiyan, Rajendra D; Baron, David; Thanos, Panayotis K; Colon-Perez, Luis M; Demortrovics, Zsolt; Gold, Mark S

2017-01-01

Reward deficiency syndrome (RDS) was first proposed by Kenneth Blum in 1995 to provide a clinically relevant and predictive term for conditions involving deficits in mesocorticolimbic dopamine function. Genetic, molecular, and neuronal alterations in key components of this circuitry contribute to a reward deficit state that can drive drug-seeking, consumption, and relapse. Among the dysfunctions observed in RDS are dysregulated resting state networks, which recently have been assessed in detail in chronic drug users by, positron emission tomography, functional magnetic resonance imaging, and functional connectivity analysis. A growing number of studies are helping to determine the putative roles of dopamine and glutamatergic neurotransmission in the regulation of activity in resting state networks, particularly in brain reward circuitry affected in drug use disorders. Indeed, we hypothesize in the present review that loss of homeostasis of these systems may lead to 'unbalanced' functional networks that might be both cause and outcome of disrupted synaptic communication between cortical and subcortical systems essential for controlling reward, emotional control, sensation seeking, and chronic drug use.

The anatomy of cognitive impairment in amyotrophic lateral sclerosis: more than frontal lobe dysfunction.

PubMed

Tsermentseli, Stella; Leigh, P Nigel; Goldstein, Laura H

2012-02-01

Cognitive and behavioural impairments accompanying amyotrophic lateral sclerosis (ALS) have been reported since the early 20th century. Typically, these changes can be associated with a dysexecutive syndrome or manifest as a frontotemporal dementia (FTD). Although the nature of specific frontotemporal dysfunction in ALS remains to be refined, as with the clinical presentation, there is likely to be significant heterogeneity. This article will review the current state of knowledge regarding the neuropathological and neuroanatomical basis for cognitive dysfunction in ALS. Neuropathological findings suggest that ALS does not selectively affect the frontotemporal network but rather is part of a broad clinico-pathological spectrum now known as TAR-DNA binding protein (TDP)-43 proteinopathies. Functional neuroimaging has supported neuropsychological findings of frontotemporal dysfunction but has also implied the involvement of somatosensory areas. Structural neuroimaging has not been able to establish a specific hypothesis of extra-motor cortical atrophy beyond the combination of various frontal, temporal and limbic areas. The finding of reduction in the integrity of white matter in the frontal, temporal and parietal lobes including long association fibers suggests that subcortical involvement may underlie both cognitive and functional changes in ALS. Future perspectives for further investigations are highlighted. Copyright © 2011 Elsevier Srl. All rights reserved.

Dissociable changes in functional network topology underlie early category learning and development of automaticity

PubMed Central

Soto, Fabian A.; Bassett, Danielle S.; Ashby, F. Gregory

2016-01-01

Recent work has shown that multimodal association areas–including frontal, temporal and parietal cortex–are focal points of functional network reconfiguration during human learning and performance of cognitive tasks. On the other hand, neurocomputational theories of category learning suggest that the basal ganglia and related subcortical structures are focal points of functional network reconfiguration during early learning of some categorization tasks, but become less so with the development of automatic categorization performance. Using a combination of network science and multilevel regression, we explore how changes in the connectivity of small brain regions can predict behavioral changes during training in a visual categorization task. We find that initial category learning, as indexed by changes in accuracy, is predicted by increasingly efficient integrative processing in subcortical areas, with higher functional specialization, more efficient integration across modules, but a lower cost in terms of redundancy of information processing. The development of automaticity, as indexed by changes in the speed of correct responses, was predicted by lower clustering (particularly in subcortical areas), higher strength (highest in cortical areas) and higher betweenness centrality. By combining neurocomputational theories and network scientific methods, these results synthesize the dissociative roles of multimodal association areas and subcortical structures in the development of automaticity during category learning. PMID:27453156

Dysphagia in supratentorial recent small subcortical infarcts results from bilateral pyramidal tract damage.

PubMed

Fandler, Simon; Gattringer, Thomas; Pinter, Daniela; Pirpamer, Lukas; Borsodi, Florian; Eppinger, Sebastian; Niederkorn, Kurt; Enzinger, Christian; Fazekas, Franz

2018-01-01

Background Dysphagia occurs in up to 20% of patients with a recent small subcortical infarct, even when excluding brainstem infarcts. Aim To examine the impact of lesion topography and concomitant cerebrovascular lesions on the occurrence of dysphagia in patients with a single supratentorial recent small subcortical infarct. Methods We retrospectively identified all inpatients with magnetic resonance imaging-confirmed supratentorial recent small subcortical infarcts over a five-year period. Dysphagia was determined by speech-language therapists. Recent small subcortical infarcts were compiled into a standard brain model and compared using lesion probability maps. Furthermore, magnetic resonance imaging scans were reviewed for the combination of both acute and old cerebrovascular lesions. Results A total of 243 patients with a recent small subcortical infarct were identified (mean age 67.9 ± 12.2 years). Of those, 29 had mild and 18 moderate-to-severe dysphagia. Lesion probability maps suggested no recent small subcortical infarct location favoring the occurrence of moderate-to-severe dysphagia. However, patients with moderate-to-severe dysphagia more frequently showed combined damage to both pyramidal tracts by the recent small subcortical infarct and a contralateral old lesion (lacune: 77.8% vs. 19.9%, p < 0.001; lacune or confluent white matter hyperintensities: 100% vs. 57.7%, p < 0.001) than patients without swallowing dysfunction. Comparable results were obtained when analyzing patients with any degree of dysphagia. Conclusions Preexisting contralateral vascular pyramidal tract lesions are closely related to the occurrence of moderate-to-severe dysphagia in patients with supratentorial recent small subcortical infarcts.

Consciousness and epilepsy: why are complex-partial seizures complex?

PubMed Central

Englot, Dario J.; Blumenfeld, Hal

2010-01-01

Why do complex-partial seizures in temporal lobe epilepsy (TLE) cause a loss of consciousness? Abnormal function of the medial temporal lobe is expected to cause memory loss, but it is unclear why profoundly impaired consciousness is so common in temporal lobe seizures. Recent exciting advances in behavioral, electrophysiological, and neuroimaging techniques spanning both human patients and animal models may allow new insights into this old question. While behavioral automatisms are often associated with diminished consciousness during temporal lobe seizures, impaired consciousness without ictal motor activity has also been described. Some have argued that electrographic lateralization of seizure activity to the left temporal lobe is most likely to cause impaired consciousness, but the evidence remains equivocal. Other data correlates ictal consciousness in TLE with bilateral temporal lobe involvement of seizure spiking. Nevertheless, it remains unclear why bilateral temporal seizures should impair responsiveness. Recent evidence has shown that impaired consciousness during temporal lobe seizures is correlated with large-amplitude slow EEG activity and neuroimaging signal decreases in the frontal and parietal association cortices. This abnormal decreased function in the neocortex contrasts with fast polyspike activity and elevated cerebral blood flow in limbic and other subcortical structures ictally. Our laboratory has thus proposed the “network inhibition hypothesis,” in which seizure activity propagates to subcortical regions necessary for cortical activation, allowing the cortex to descend into an inhibited state of unconsciousness during complex-partial temporal lobe seizures. Supporting this hypothesis, recent rat studies during partial limbic seizures have shown that behavioral arrest is associated with frontal cortical slow waves, decreased neuronal firing, and hypometabolism. Animal studies further demonstrate that cortical deactivation and behavioral changes depend on seizure spread to subcortical structures including the lateral septum. Understanding the contributions of network inhibition to impaired consciousness in TLE is an important goal, as recurrent limbic seizures often result in cortical dysfunction during and between epileptic events that adversely affects patients’ quality of life. PMID:19818900

Thalamus and Language: What do we know from vascular and degenerative pathologies.

PubMed

Moretti, Rita; Caruso, Paola; Crisman, Elena; Gazzin, Silvia

2018-01-01

Language is a complex cognitive task that is essential in our daily life. For decades, researchers have tried to understand the different role of cortical and subcortical areas in cerebral language representations and language processing. Language-related cortical zones are richly interconnected with other cortical regions (particularly via myelinated fibre tracts), but they also participate in subcortical feedback loops within the basal ganglia (caudate nucleus and putamen) and thalamus. The most relevant thalamic functions are the control and adaptation of cortico-cortical connectivity and bandwidth for information exchange. Despite having the knowledge of thalamic and basal ganglionic involvement in linguistic operations, the specific functions of these subcortical structures remain rather controversial. The aim of this study is to better understand the role of thalamus in language network, exploring the functional configuration of basal network components. The language specificity of subcortical supporting activity and the associated clinical features in thalamic involvement are also highlighted.

Functional and clinical neuroanatomy of morality.

PubMed

Fumagalli, Manuela; Priori, Alberto

2012-07-01

Morality is among the most sophisticated features of human judgement, behaviour and, ultimately, mind. An individual who behaves immorally may violate ethical rules and civil rights, and may threaten others' individual liberty, sometimes becoming violent and aggressive. In recent years, neuroscience has shown a growing interest in human morality, and has advanced our understanding of the cognitive and emotional processes involved in moral decisions, their anatomical substrates and the neurology of abnormal moral behaviour. In this article, we review research findings that have provided a key insight into the functional and clinical neuroanatomy of the brain areas involved in normal and abnormal moral behaviour. The 'moral brain' consists of a large functional network including both cortical and subcortical anatomical structures. Because morality is a complex process, some of these brain structures share their neural circuits with those controlling other behavioural processes, such as emotions and theory of mind. Among the anatomical structures implicated in morality are the frontal, temporal and cingulate cortices. The prefrontal cortex regulates activity in subcortical emotional centres, planning and supervising moral decisions, and when its functionality is altered may lead to impulsive aggression. The temporal lobe is involved in theory of mind and its dysfunction is often implicated in violent psychopathy. The cingulate cortex mediates the conflict between the emotional and the rational components of moral reasoning. Other important structures contributing to moral behaviour include the subcortical nuclei such as the amygdala, hippocampus and basal ganglia. Brain areas participating in moral processing can be influenced also by genetic, endocrine and environmental factors. Hormones can modulate moral behaviour through their effects on the brain. Finally, genetic polymorphisms can predispose to aggressivity and violence, arguing for a genetic-based predisposition to morality. Because abnormal moral behaviour can arise from both functional and structural brain abnormalities that should be diagnosed and treated, the neurology of moral behaviour has potential implications for clinical practice and raises ethical concerns. Last, since research has developed several neuromodulation techniques to improve brain dysfunction (deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation), knowing more about the 'moral brain' might help to develop novel therapeutic strategies for neurologically based abnormal moral behaviour.

Pharmacological modulation of pulvinar resting-state regional oscillations and network dynamics in major depression

PubMed Central

Tadayonnejad, Reza; Ajilore, Olusola; Mickey, Brian J.; Crane, Natania A.; Hsu, David T.; Kumar, Anand; Zubieta, Jon-Kar; Langenecker, Scott A.

2016-01-01

The pulvinar, the largest thalamus nucleus, has rich anatomical connections with several different cortical and subcortical regions suggesting its important involvement in high-level cognitive and emotional functions. Unfortunately, pulvinar dysfunction in psychiatric disorders particularly major depression disorder has not been thoroughly examined to date. In this study we explored the alterations in the baseline regional and network activities of the pulvinar in MDD by applying spectral analysis of resting-state oscillatory activity, functional connectivity and directed (effective) connectivity on resting-state fMRI data acquired from 20 healthy controls and 19 participants with MDD. Furthermore, we tested how pharmacological treatment with duloxetine can modulate the measured local and network variables in ten participants who completed treatment. Our results revealed a frequency-band dependent modulation of power spectrum characteristics of pulvinar regional oscillatory activity. At the network level, we found MDD is associated with aberrant causal interactions between pulvinar and several systems including default-mode and posterior insular networks. It was also shown that duloxetine treatment can correct or overcompensate the pathologic network behavior of the pulvinar. In conclusion, we suggest that pulvinar regional baseline oscillatory activity and its resting-state network dynamics are compromised in MDD and can be modulated therapeutically by pharmacological treatment. PMID:27148894

White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

PubMed

Craggs, Lucinda J L; Yamamoto, Yumi; Ihara, Masafumi; Fenwick, Richard; Burke, Matthew; Oakley, Arthur E; Roeber, Sigrun; Duering, Marco; Kretzschmar, Hans; Kalaria, Raj N

2014-08-01

Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM. We used post-mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro-caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles. The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P<0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P<0.01), with most prominent axonal abnormalities observed in the frontal WM (P<0.05). The SIs of arterioles in CADASIL were increased by 25-45% throughout the regions assessed, with the highest change in the mid-frontal region (P=0.000). Our results suggest disruption of either cortico-cortical or subcortical-cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures. © 2013 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Altered intra- and inter-network functional coupling of resting-state networks associated with motor dysfunction in stroke.

PubMed

Zhao, Zhiyong; Wu, Jie; Fan, Mingxia; Yin, Dazhi; Tang, Chaozheng; Gong, Jiayu; Xu, Guojun; Gao, Xinjie; Yu, Qiurong; Yang, Hao; Sun, Limin; Jia, Jie

2018-04-24

Motor functions are supported through functional integration across the extended motor system network. Individuals following stroke often show deficits on motor performance requiring coordination of multiple brain networks; however, the assessment of connectivity patterns after stroke was still unclear. This study aimed to investigate the changes in intra- and inter-network functional connectivity (FC) of multiple networks following stroke and further correlate FC with motor performance. Thirty-three left subcortical chronic stroke patients and 34 healthy controls underwent resting-state functional magnetic resonance imaging. Eleven resting-state networks were identified via independent component analysis (ICA). Compared with healthy controls, the stroke group showed abnormal FC within the motor network (MN), visual network (VN), dorsal attention network (DAN), and executive control network (ECN). Additionally, the FC values of the ipsilesional inferior parietal lobule (IPL) within the ECN were negatively correlated with the Fugl-Meyer Assessment (FMA) scores (hand + wrist). With respect to inter-network interactions, the ipsilesional frontoparietal network (FPN) decreased FC with the MN and DAN; the contralesional FPN decreased FC with the ECN, but it increased FC with the default mode network (DMN); and the posterior DMN decreased FC with the VN. In sum, this study demonstrated the coexistence of intra- and inter-network alterations associated with motor-visual attention and high-order cognitive control function in chronic stroke, which might provide insights into brain network plasticity following stroke. © 2018 Wiley Periodicals, Inc.

Shifted dynamic interactions between subcortical nuclei and inferior frontal gyri during response preparation in persistent developmental stuttering.

PubMed

Metzger, F Luise; Auer, Tibor; Helms, Gunther; Paulus, Walter; Frahm, Jens; Sommer, Martin; Neef, Nicole E

2018-01-01

Persistent developmental stuttering is associated with basal ganglia dysfunction or dopamine dysregulation. Here, we studied whole-brain functional connectivity to test how basal ganglia structures coordinate and reorganize sensorimotor brain networks in stuttering. To this end, adults who stutter and fluent speakers (control participants) performed a response anticipation paradigm in the MRI scanner. The preparation of a manual Go/No-Go response reliably produced activity in the basal ganglia and thalamus and particularly in the substantia nigra. Strikingly, in adults who stutter, substantia nigra activity correlated positively with stuttering severity. Furthermore, functional connectivity analyses yielded altered task-related network formations in adults who stutter compared to fluent speakers. Specifically, in adults who stutter, the globus pallidus and the thalamus showed increased network synchronization with the inferior frontal gyrus. This implies dynamic shifts in the response preparation-related network organization through the basal ganglia in the context of a non-speech motor task in stuttering. Here we discuss current findings in the traditional framework of how D1 and D2 receptor activity shapes focused movement selection, thereby suggesting a disproportional involvement of the direct and the indirect pathway in stuttering.

“Low road” to rehabilitation: a perspective on subliminal sensory neuroprosthetics

PubMed Central

Ghai, Shashank; Ghai, Ishan; Effenberg, Alfred O

2018-01-01

Fear can propagate parallelly through both cortical and subcortical pathways. It can instigate memory consolidation habitually and might allow internal simulation of movements independent of the cortical structures. This perspective suggests delivery of subliminal, aversive and kinematic audiovisual stimuli via neuroprosthetics in patients with neocortical dysfunctions. We suggest possible scenarios by which these stimuli might bypass damaged neocortical structures and possibly assisting in motor relearning. Anticipated neurophysiological mechanisms and methodological scenarios have been discussed in this perspective. This approach introduces novel perspectives into neuropsychology as to how subcortical pathways might be used to induce motor relearning. PMID:29398914

Pathological Joking or Witzelsucht Revisited.

PubMed

Granadillo, Elias D; Mendez, Mario F

2016-01-01

Humor, or the perception or elicitation of mirth and funniness, is distinguishable from laughter and can be differentially disturbed by neuropsychiatric disease. The authors describe two patients with constant joking, or Witzelsucht, in the absence of pseudobulbar affect and review the literature on pathological humor. These patients had involvement of frontal structures, impaired appreciation of nonsimple humor, and a compulsion for disinhibited joking. Current neuroscience suggests that impaired humor integration from right lateral frontal injury and disinhibition from orbitofrontal damage results in disinhibited humor, preferentially activating limbic and subcortical reward centers. Additional frontal-subcortical circuit dysfunction may promote pathological joking as a compulsion.

PATHOLOGICAL JOKING OR WITZELSUCHT REVISITED

PubMed Central

Granadillo, Elias; Mendez, Mario F.

2018-01-01

Humor, or the perception or elicitation of mirth and funniness, is distinguishable from laughter and can be differentially disturbed by neuropsychiatric disease. We present two patients with constant joking, or Witzelsucht, in the absence of pseudobulbar affect and review the literature on pathological humor. These patients had involvement of frontal structures, impaired appreciation of non-simple humor, and a compulsion for disinhibited joking. Current neuroscience suggests impaired humor integration from right lateral frontal injury and disinhibition from orbitofrontal damage results in disinhibited humor preferentially activating limbic and subcortical reward centers. Additional frontal-subcortical circuit dysfunction may promote pathological joking as a compulsion. PMID:26900737

"Low road" to rehabilitation: a perspective on subliminal sensory neuroprosthetics.

PubMed

Ghai, Shashank; Ghai, Ishan; Effenberg, Alfred O

2018-01-01

Fear can propagate parallelly through both cortical and subcortical pathways. It can instigate memory consolidation habitually and might allow internal simulation of movements independent of the cortical structures. This perspective suggests delivery of subliminal, aversive and kinematic audiovisual stimuli via neuroprosthetics in patients with neocortical dysfunctions. We suggest possible scenarios by which these stimuli might bypass damaged neocortical structures and possibly assisting in motor relearning. Anticipated neurophysiological mechanisms and methodological scenarios have been discussed in this perspective. This approach introduces novel perspectives into neuropsychology as to how subcortical pathways might be used to induce motor relearning.

Subcortical atrophy is associated with cognitive impairment in mild Parkinson disease: a combined investigation of volumetric changes, cortical thickness, and vertex-based shape analysis.

PubMed

Mak, E; Bergsland, N; Dwyer, M G; Zivadinov, R; Kandiah, N

2014-12-01

The involvement of subcortical deep gray matter and cortical thinning associated with mild Parkinson disease remains poorly understood. We assessed cortical thickness and subcortical volumes in patients with Parkinson disease without dementia and evaluated their associations with cognitive dysfunction. The study included 90 patients with mild Parkinson disease without dementia. Neuropsychological assessments classified the sample into patients with mild cognitive impairment (n = 25) and patients without cognitive impairment (n = 65). Volumetric data for subcortical structures were obtained by using the FMRIB Integrated Registration and Segmentation Tool while whole-brain, gray and white matter volumes were estimated by using Structural Image Evaluation, with Normalization of Atrophy. Vertex-based shape analyses were performed to investigate shape differences in subcortical structures. Vertex-wise group differences in cortical thickness were also assessed. Volumetric comparisons between Parkinson disease with mild cognitive impairment and Parkinson disease with no cognitive impairment were performed by using ANCOVA. Associations of subcortical structures with both cognitive function and disease severity were assessed by using linear regression models. Compared with Parkinson disease with no cognitive impairment, Parkinson disease with mild cognitive impairment demonstrated reduced volumes of the thalamus (P = .03) and the nucleus accumbens (P = .04). Significant associations were found for the nucleus accumbens and putamen with performances on the attention/working memory domains (P < .05) and nucleus accumbens and language domains (P = .04). The 2 groups did not differ in measures of subcortical shape or in cortical thickness. Patients with Parkinson disease with mild cognitive impairment demonstrated reduced subcortical volumes, which were associated with cognitive deficits. The thalamus, nucleus accumbens, and putamen may serve as potential biomarkers for Parkinson disease-mild cognitive impairment. © 2014 by American Journal of Neuroradiology.

Multiple cortical thickness sub-networks and cognitive impairments in first episode, drug naïve patients with late life depression: A graph theory analysis.

PubMed

Shin, Jeong-Hyeon; Um, Yu Hyun; Lee, Chang Uk; Lim, Hyun Kook; Seong, Joon-Kyung

2018-03-15

Coordinated and pattern-wise changes in large scale gray matter structural networks reflect neural circuitry dysfunction in late life depression (LLD), which in turn is associated with emotional dysregulation and cognitive impairments. However, due to methodological limitations, there have been few attempts made to identify individual-level structural network properties or sub-networks that are involved in important brain functions in LLD. In this study, we sought to construct individual-level gray matter structural networks using average cortical thicknesses of several brain areas to investigate the characteristics of the gray matter structural networks in normal controls and LLD patients. Additionally, we investigated the structural sub-networks correlated with several clinical measurements including cognitive impairment and depression severity. We observed that small worldness, clustering coefficients, global and local efficiency, and hub structures in the brains of LLD patients were significantly different from healthy controls. We further found that a sub-network including the anterior cingulate, dorsolateral prefrontal cortex and superior prefrontal cortex is significantly associated with attention control and executive function. The severity of depression was associated with the sub-networks comprising the salience network, including the anterior cingulate and insula. We investigated cortico-cortical connectivity, but omitted the subcortical structures such as the striatum and thalamus. We report differences in patterns between several clinical measurements and sub-networks from large-scale and individual-level cortical thickness networks in LLD. Copyright © 2018 Elsevier B.V. All rights reserved.

Dynamics of Intersubject Brain Networks during Anxious Anticipation

PubMed Central

Najafi, Mahshid; Kinnison, Joshua; Pessoa, Luiz

2017-01-01

How do large-scale brain networks reorganize during the waxing and waning of anxious anticipation? Here, threat was dynamically modulated during human functional MRI as two circles slowly meandered on the screen; if they touched, an unpleasant shock was delivered. We employed intersubject correlation analysis, which allowed the investigation of network-level functional connectivity across brains, and sought to determine how network connectivity changed during periods of approach (circles moving closer) and periods of retreat (circles moving apart). Analysis of positive connection weights revealed that dynamic threat altered connectivity within and between the salience, executive, and task-negative networks. For example, dynamic functional connectivity increased within the salience network during approach and decreased during retreat. The opposite pattern was found for the functional connectivity between the salience and task-negative networks: decreases during approach and increases during approach. Functional connections between subcortical regions and the salience network also changed dynamically during approach and retreat periods. Subcortical regions exhibiting such changes included the putative periaqueductal gray, putative habenula, and putative bed nucleus of the stria terminalis. Additional analysis of negative functional connections revealed dynamic changes, too. For example, negative weights within the salience network decreased during approach and increased during retreat, opposite what was found for positive weights. Together, our findings unraveled dynamic features of functional connectivity of large-scale networks and subcortical regions across participants while threat levels varied continuously, and demonstrate the potential of characterizing emotional processing at the level of dynamic networks. PMID:29209184

Grey matter volume loss is associated with specific clinical motor signs in Huntington's disease.

PubMed

Coppen, Emma M; Jacobs, Milou; van den Berg-Huysmans, Annette A; van der Grond, Jeroen; Roos, Raymund A C

2018-01-01

Motor disturbances are clinical hallmarks of Huntington's disease (HD) and involve chorea, dystonia, hypokinesia and visuomotor dysfunction. Investigating the association between specific motor signs and different regional volumes is important to understand the heterogeneity of HD. To investigate the motor phenotype of HD and associations with subcortical and cortical grey matter volume loss. Structural T1-weighted MRI scans of 79 HD patients and 30 healthy controls were used to calculate volumes of seven subcortical structures including the nucleus accumbens, hippocampus, thalamus, caudate nucleus, putamen, pallidum and amygdala. Multiple linear regression analyses, corrected for age, gender, CAG, MRI scan protocol and normalized brain volume, were performed to assess the relationship between subcortical volumes and different motor subdomains (i.e. eye movements, chorea, dystonia, hypokinesia/rigidity and gait/balance). Voxel-based morphometry analysis was used to investigate the relationship between cortical volume changes and motor signs. Subcortical volume loss of the accumbens nucleus, caudate nucleus, putamen, and pallidum were associated with higher chorea scores. No other subcortical region was significantly associated with motor symptoms after correction for multiple comparisons. Voxel-based cortical grey matter volume reductions in occipital regions were related with an increase in eye movement scores. In HD, chorea is mainly associated with subcortical volume loss, while eye movements are more related to cortical volume loss. Both subcortical and cortical degeneration has an impact on motor impairment in HD. This implies that there is a widespread contribution of different brain regions resulting in the clinical motor presentation seen in HD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural network efficiency is associated with cognitive impairment in small-vessel disease.

PubMed

Lawrence, Andrew J; Chung, Ai Wern; Morris, Robin G; Markus, Hugh S; Barrick, Thomas R

2014-07-22

To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment. A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested. Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed. Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies. © 2014 American Academy of Neurology.

Structural network efficiency is associated with cognitive impairment in small-vessel disease

PubMed Central

Chung, Ai Wern; Morris, Robin G.; Markus, Hugh S.; Barrick, Thomas R.

2014-01-01

Objective: To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment. Methods: A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested. Results: Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed. Conclusions: Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies. PMID:24951477

Inattention Predicts Increased Thickness of Left Occipital Cortex in Men with Attention-Deficit/Hyperactivity Disorder.

PubMed

Sörös, Peter; Bachmann, Katharina; Lam, Alexandra P; Kanat, Manuela; Hoxhaj, Eliza; Matthies, Swantje; Feige, Bernd; Müller, Helge H O; Thiel, Christiane; Philipsen, Alexandra

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) in adulthood is a serious and frequent psychiatric disorder with the core symptoms inattention, impulsivity, and hyperactivity. The principal aim of this study was to investigate associations between brain morphology, i.e., cortical thickness and volumes of subcortical gray matter, and individual symptom severity in adult ADHD. Surface-based brain morphometry was performed in 35 women and 29 men with ADHD using FreeSurfer. Linear regressions were calculated between cortical thickness and the volumes of subcortical gray matter and the inattention, hyperactivity, and impulsivity subscales of the Conners Adult ADHD Rating Scales (CAARS). Two separate analyses were performed. For the first analysis, age was included as additional regressor. For the second analysis, both age and severity of depression were included as additional regressors. Study participants were recruited between June 2012 and January 2014. Linear regression identified an area in the left occipital cortex of men, covering parts of the middle occipital sulcus and gyrus, in which the score on the CAARS inattention subscale predicted increased mean cortical thickness [ F (1,27) = 26.27, p  < 0.001, adjusted R 2  = 0.4744]. No significant associations were found between cortical thickness and the scores on CAARS subscales in women. No significant associations were found between the volumes of subcortical gray matter and the scores on CAARS subscales, neither in men nor in women. These results remained stable when severity of depression was included as additional regressor, together with age. Increased cortical thickness in the left occipital cortex may represent a mechanism to compensate for dysfunctional attentional networks in male adult ADHD patients.

Aberrant topological patterns of brain structural network in temporal lobe epilepsy.

PubMed

Yasuda, Clarissa Lin; Chen, Zhang; Beltramini, Guilherme Coco; Coan, Ana Carolina; Morita, Marcia Elisabete; Kubota, Bruno; Bergo, Felipe; Beaulieu, Christian; Cendes, Fernando; Gross, Donald William

2015-12-01

Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy. We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches. We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE. These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Neural substrates of decision-making.

PubMed

Broche-Pérez, Y; Herrera Jiménez, L F; Omar-Martínez, E

2016-06-01

Decision-making is the process of selecting a course of action from among 2 or more alternatives by considering the potential outcomes of selecting each option and estimating its consequences in the short, medium and long term. The prefrontal cortex (PFC) has traditionally been considered the key neural structure in decision-making process. However, new studies support the hypothesis that describes a complex neural network including both cortical and subcortical structures. The aim of this review is to summarise evidence on the anatomical structures underlying the decision-making process, considering new findings that support the existence of a complex neural network that gives rise to this complex neuropsychological process. Current evidence shows that the cortical structures involved in decision-making include the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). This process is assisted by subcortical structures including the amygdala, thalamus, and cerebellum. Findings to date show that both cortical and subcortical brain regions contribute to the decision-making process. The neural basis of decision-making is a complex neural network of cortico-cortical and cortico-subcortical connections which includes subareas of the PFC, limbic structures, and the cerebellum. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Transient synchronization of hippocampo-striato-thalamo-cortical networks during sleep spindle oscillations induces motor memory consolidation.

PubMed

Boutin, Arnaud; Pinsard, Basile; Boré, Arnaud; Carrier, Julie; Fogel, Stuart M; Doyon, Julien

2018-04-01

Sleep benefits motor memory consolidation. This mnemonic process is thought to be mediated by thalamo-cortical spindle activity during NREM-stage2 sleep episodes as well as changes in striatal and hippocampal activity. However, direct experimental evidence supporting the contribution of such sleep-dependent physiological mechanisms to motor memory consolidation in humans is lacking. In the present study, we combined EEG and fMRI sleep recordings following practice of a motor sequence learning (MSL) task to determine whether spindle oscillations support sleep-dependent motor memory consolidation by transiently synchronizing and coordinating specialized cortical and subcortical networks. To that end, we conducted EEG source reconstruction on spindle epochs in both cortical and subcortical regions using novel deep-source localization techniques. Coherence-based metrics were adopted to estimate functional connectivity between cortical and subcortical structures over specific frequency bands. Our findings not only confirm the critical and functional role of NREM-stage2 sleep spindles in motor skill consolidation, but provide first-time evidence that spindle oscillations [11-17 Hz] may be involved in sleep-dependent motor memory consolidation by locally reactivating and functionally binding specific task-relevant cortical and subcortical regions within networks including the hippocampus, putamen, thalamus and motor-related cortical regions. Copyright © 2018 Elsevier Inc. All rights reserved.

Altered structural brain changes and neurocognitive performance in pediatric HIV.

PubMed

Yadav, Santosh K; Gupta, Rakesh K; Garg, Ravindra K; Venkatesh, Vimala; Gupta, Pradeep K; Singh, Alok K; Hashem, Sheema; Al-Sulaiti, Asma; Kaura, Deepak; Wang, Ena; Marincola, Francesco M; Haris, Mohammad

2017-01-01

Pediatric HIV patients often suffer with neurodevelopmental delay and subsequently cognitive impairment. While tissue injury in cortical and subcortical regions in the brain of adult HIV patients has been well reported there is sparse knowledge about these changes in perinatally HIV infected pediatric patients. We analyzed cortical thickness, subcortical volume, structural connectivity, and neurocognitive functions in pediatric HIV patients and compared with those of pediatric healthy controls. With informed consent, 34 perinatally infected pediatric HIV patients and 32 age and gender matched pediatric healthy controls underwent neurocognitive assessment and brain magnetic resonance imaging (MRI) on a 3 T clinical scanner. Altered cortical thickness, subcortical volumes, and abnormal neuropsychological test scores were observed in pediatric HIV patients. The structural network connectivity analysis depicted lower connection strengths, lower clustering coefficients, and higher path length in pediatric HIV patients than healthy controls. The network betweenness and network hubs in cortico-limbic regions were distorted in pediatric HIV patients. The findings suggest that altered cortical and subcortical structures and regional brain connectivity in pediatric HIV patients may contribute to deficits in their neurocognitive functions. Further, longitudinal studies are required for better understanding of the effect of HIV pathogenesis on brain structural changes throughout the brain development process under standard ART treatment.

Time Processing in Children with Tourette's Syndrome

ERIC Educational Resources Information Center

Vicario, Carmelo Mario; Martino, Davide; Spata, Felice; Defazio, Giovanni; Giacche, Roberta; Martino, Vito; Rappo, Gaetano; Pepi, Anna Maria; Silvestri, Paola Rosaria; Cardona, Francesco

2010-01-01

Background: Tourette syndrome (TS) is characterized by dysfunctional connectivity between prefrontal cortex and sub-cortical structures, and altered meso-cortical and/or meso-striatal dopamine release. Since time processing is also regulated by fronto-striatal circuits and modulated by dopaminergic transmission, we hypothesized that time…

Formulaic Language in Parkinson's Disease and Alzheimer's Disease: Complementary Effects of Subcortical and Cortical Dysfunction

PubMed Central

Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy

2015-01-01

Purpose The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of formulaic language. Persons with Parkinson's disease (PD), having dysfunctional basal ganglia, were predicted to show impoverished formulaic expressions in contrast to speakers with AD. This study compared participants with PD, participants with AD, and healthy control (HC) participants on protocols probing production and comprehension of formulaic expressions. Method Spontaneous speech samples were recorded from 16 individuals with PD, 12 individuals with AD, and 18 HC speakers. Structured tests were then administered as probes of comprehension. Results The PD group had lower proportions of formulaic expressions compared with the AD and HC groups. Comprehension testing yielded opposite contrasts: participants with PD showed significantly higher performance compared with participants with AD and did not differ from HC participants. Conclusions The finding that PD produced lower proportions of formulaic expressions compared with AD and HC supports the view that subcortical nuclei modulate the production of formulaic expressions. Contrasting results on formal testing of comprehension, whereby participants with AD performed significantly worse than participants with PD and HC participants, indicate differential effects on procedural and declarative knowledge associated with these neurological conditions. PMID:26183940

Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

PubMed

Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

2018-01-01

Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  < 0.01) mainly involved the orbitofrontal, parietal, and temporal cortices, as well as the basal ganglia. The brain connectivity network was progressively disrupted as cognitive impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

Motor Recovery After Subcortical Stroke Depends on Modulation of Extant Motor Networks.

PubMed

Sharma, Nikhil; Baron, Jean-Claude

2015-01-01

Stroke is the leading cause of long-term disability. Functional imaging studies report widespread changes in movement-related cortical networks after stroke. Whether these are a result of stroke-specific cognitive processes or reflect modulation of existing movement-related networks is unknown. Understanding this distinction is critical in establishing more effective restorative therapies after stroke. Using multivariate analysis (tensor-independent component analysis - TICA), we map the neural networks involved during motor imagery (MI) and executed movement (EM) in subcortical stroke patients and age-matched controls. Twenty subcortical stroke patients and 17 age-matched controls were recruited. They were screened for their ability to carry out MI (Chaotic MI Assessment). The fMRI task was a right-hand finger-thumb opposition sequence (auditory-paced 1 Hz; 2, 3, 4, 5, 2…). Two separate runs were acquired (MI and rest and EM and rest; block design). There was no distinction between groups or tasks until the last stage of analysis, which allowed TICA to identify independent components (ICs) that were common or distinct to each group or task with no prior assumptions. TICA defined 28 ICs. ICs representing artifacts were excluded. ICs were only included if the subject scores were significant (for either EM or MI). Seven ICs remained that involved the primary and secondary motor networks. All ICs were shared between the stroke and age-matched controls. Five ICs were common to both tasks and three were exclusive to EM. Two ICs were related to motor recovery and one with time since stroke onset, but all were shared with age-matched controls. No IC was exclusive to stroke patients. We report that the cortical networks in stroke patients that relate to recovery of motor function represent modulation of existing cortical networks present in age-matched controls. The absence of cortical networks specific to stroke patients suggests that motor adaptation and other potential confounders (e.g., effort and additional muscle use) are not responsible for the changes in the cortical networks reported after stroke. This highlights that recovery of motor function after subcortical stroke involves preexisting cortical networks that could help identify more effective restorative therapies.

Gestational Age is Dimensionally Associated with Structural Brain Network Abnormalities Across Development.

PubMed

Nassar, Rula; Kaczkurkin, Antonia N; Xia, Cedric Huchuan; Sotiras, Aristeidis; Pehlivanova, Marieta; Moore, Tyler M; Garcia de La Garza, Angel; Roalf, David R; Rosen, Adon F G; Lorch, Scott A; Ruparel, Kosha; Shinohara, Russell T; Davatzikos, Christos; Gur, Ruben C; Gur, Raquel E; Satterthwaite, Theodore D

2018-04-21

Prematurity is associated with diverse developmental abnormalities, yet few studies relate cognitive and neurostructural deficits to a dimensional measure of prematurity. Leveraging a large sample of children, adolescents, and young adults (age 8-22 years) studied as part of the Philadelphia Neurodevelopmental Cohort, we examined how variation in gestational age impacted cognition and brain structure later in development. Participants included 72 preterm youth born before 37 weeks' gestation and 206 youth who were born at term (37 weeks or later). Using a previously-validated factor analysis, cognitive performance was assessed in three domains: (1) executive function and complex reasoning, (2) social cognition, and (3) episodic memory. All participants completed T1-weighted neuroimaging at 3 T to measure brain volume. Structural covariance networks were delineated using non-negative matrix factorization, an advanced multivariate analysis technique. Lower gestational age was associated with both deficits in executive function and reduced volume within 11 of 26 structural covariance networks, which included orbitofrontal, temporal, and parietal cortices as well as subcortical regions including the hippocampus. Notably, the relationship between lower gestational age and executive dysfunction was accounted for in part by structural network deficits. Together, these findings emphasize the durable impact of prematurity on cognition and brain structure, which persists across development.

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

PubMed Central

Batla, Amit; Bhatia, Kailash; Dauer, William T; Dresel, Christian; Niethammer, Martin; Eidelberg, David; Raike, Robert S.; Smith, Yoland; Jinnah, H. A.; Hess, Ellen J.; Meunier, Sabine; Hallett, Mark; Fremont, Rachel; Khodakhah, Kamran; LeDoux, Mark S.; Popa, Traian; Gallea, Cécile; Lehericy, Stéphane; Bostan, Andreea C.; Strick, Peter L.

2016-01-01

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed: The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia.Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia.Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include: Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems.Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin. PMID:27734238

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia.

PubMed

Shakkottai, Vikram G; Batla, Amit; Bhatia, Kailash; Dauer, William T; Dresel, Christian; Niethammer, Martin; Eidelberg, David; Raike, Robert S; Smith, Yoland; Jinnah, H A; Hess, Ellen J; Meunier, Sabine; Hallett, Mark; Fremont, Rachel; Khodakhah, Kamran; LeDoux, Mark S; Popa, Traian; Gallea, Cécile; Lehericy, Stéphane; Bostan, Andreea C; Strick, Peter L

2017-04-01

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed: The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia. Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia. Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include: Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems. Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin.

Review of thalamocortical resting-state fMRI studies in schizophrenia

PubMed Central

Giraldo-Chica, Monica; Woodward, Neil D.

2017-01-01

Brain circuitry underlying cognition, emotion, and perception is abnormal in schizophrenia. There is considerable evidence that the neuropathology of schizophrenia includes the thalamus, a key hub of cortical-subcortical circuitry and an important regulator of cortical activity. However, the thalamus is a heterogeneous structure composed of several nuclei with distinct inputs and cortical connections. Limitations of conventional neuroimaging methods and conflicting findings from post-mortem investigations have made it difficult to determine if thalamic pathology in schizophrenia is widespread or limited to specific thalamocortical circuits. Resting-state fMRI has proven invaluable for understanding the large-scale functional organization of the brain and investigating neural circuitry relevant to psychiatric disorders. This article summarizes resting-state fMRI investigations of thalamocortical functional connectivity in schizophrenia. Particular attention is paid to the course, diagnostic specificity, and clinical correlates of thalamocortical network dysfunction. PMID:27531067

Creutzfeldt-Jakob disease with mixed transcortical aphasia: insights into echolalia.

PubMed

McPherson, S E; Kuratani, J D; Cummings, J L; Shih, J; Mischel, P S; Vinters, H V

1994-01-01

Aphasia is a common manifestation of Creutzfeldt-Jakob disease (CJD), and investigation of the linguistic disorders of CJD patients may provide insights into the neurobiological mechanisms of language and aphasia. We report an autopsy-confirmed case of CJD in which the presenting symptom was change in language abilities. The patient ultimately evidenced mixed transcortical aphasia (MTA) with echolalia. Disruption of frontal-subcortical circuits with environmental dependency accounts for the symptoms in MTA, including intact repetition and echolalia. Observation in this patient and a review of the literature suggest that frontal-subcortical circuit dysfunction may contribute to the syndrome of echolalia. This hypothesis offers an alternative explanation to "isolation" of the speech area as the cause of MTA.

Structural covariance networks in the mouse brain.

PubMed

Pagani, Marco; Bifone, Angelo; Gozzi, Alessandro

2016-04-01

The presence of networks of correlation between regional gray matter volume as measured across subjects in a group of individuals has been consistently described in several human studies, an approach termed structural covariance MRI (scMRI). Complementary to prevalent brain mapping modalities like functional and diffusion-weighted imaging, the approach can provide precious insights into the mutual influence of trophic and plastic processes in health and pathological states. To investigate whether analogous scMRI networks are present in lower mammal species amenable to genetic and experimental manipulation such as the laboratory mouse, we employed high resolution morphoanatomical MRI in a large cohort of genetically-homogeneous wild-type mice (C57Bl6/J) and mapped scMRI networks using a seed-based approach. We show that the mouse brain exhibits robust homotopic scMRI networks in both primary and associative cortices, a finding corroborated by independent component analyses of cortical volumes. Subcortical structures also showed highly symmetric inter-hemispheric correlations, with evidence of distributed antero-posterior networks in diencephalic regions of the thalamus and hypothalamus. Hierarchical cluster analysis revealed six identifiable clusters of cortical and sub-cortical regions corresponding to previously described neuroanatomical systems. Our work documents the presence of homotopic cortical and subcortical scMRI networks in the mouse brain, thus supporting the use of this species to investigate the elusive biological and neuroanatomical underpinnings of scMRI network development and its derangement in neuropathological states. The identification of scMRI networks in genetically homogeneous inbred mice is consistent with the emerging view of a key role of environmental factors in shaping these correlational networks. Copyright © 2016 Elsevier Inc. All rights reserved.

Alexander Disease and Megalencephalic Leukoencephalopathy with Subcortical Cysts: Leukodystrophies Arising from Astrocyte Dysfunction

ERIC Educational Resources Information Center

Gorospe, J. Rafael; Maletkovic, Jelena

2006-01-01

Disorders of white matter are some of the most commonly encountered conditions in the practice of child neurology. For a child presenting with evidence of neurological impairment, a magnetic resonance imaging (MRI) of the brain is usually performed and often proves informative in suggesting the diagnosis. Traditionally, primary white matter…

Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron (FeD)

EPA Science Inventory

Although the critical role of thyroid hormone (TH) in brain development is well established - severe deficiency producing significant neurological dysfunction - there is a paucity of data on neurological impairments that accompany modest degrees of TH disruption. Quantitative m...

Corticobasal degeneration.

PubMed

Stover, N P; Watts, R L

2001-01-01

Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative disease with both motor and cognitive dysfunction. The diagnosis is probably underestimated because of the heterogeneity of clinical features, overlap with symptoms, and pathologic findings of other neurodegenerative diseases. The most characteristic initial motor symptoms are akinesia, rigidity, and apraxia. Dystonia and alien limb phenomena are frequently observed. There is often a parkinsonian picture with failure or lack of efficacy of dopaminergic medical therapy. Cognitive decline, prompting the diagnosis of dementia, may be the most common presentation of CBD that is misdiagnosed. Pathology is characterized by an asymmetric frontoparietal neuronal loss and gliosis with ballooned, achromatic cortical neurons, nigral degeneration, and variable subcortical involvement. Neuroimaging and electrophysiologic studies may help with the diagnosis but are not specific. Treatment is primarily symptomatic and minimally effective, especially after the first several years of symptoms. CBD should be considered in the differential diagnosis of patients with motor and cognitive dysfunction presenting with cortical and subcortical features. Further studies to elucidate molecular abnormalities and biological markers associated with CBD are needed to improve clinical diagnosis and treatment of patients with this disorder.

Hyperconnective and hypoconnective cortical and subcortical functional networks in multiple system atrophy.

PubMed

Rosskopf, Johannes; Gorges, Martin; Müller, Hans-Peter; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan

2018-04-01

In multiple system atrophy (MSA), the organization of the functional brain connectivity within cortical and subcortical networks and its clinical correlates remains to be investigated. Whole-brain based 'resting-state' fMRI data were obtained from 22 MSA patients (11 MSA-C, 11 MSA-P) and 22 matched healthy controls, together with standardized clinical assessment and video-oculographic recordings (EyeLink ® ). MSA patients vs. controls showed significantly higher ponto-cerebellar functional connectivity and lower default mode network connectivity (p < .05, corrected). No differences were observed in the motor network and in the control network. The higher the ponto-cerebellar network functional connectivity was, the more pronounced was smooth pursuit impairment. This functional connectivity analysis supports a network-dependent combination of hyper- and hypoconnectivity states in MSA, in agreement with adaptive compensatory responses (hyperconnectivity) and a function disconnection syndrome (hypoconnectivity) that may occur in a consecutive sequence. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prefrontal system dysfunction and credit card debt.

PubMed

Spinella, Marcello; Yang, Bijou; Lester, David

2004-10-01

Credit card use often involves a disadvantageous allocation of finances because they allow for spending beyond means and buying on impulse. Accordingly they are associated with increased bankruptcy, anxiety, stress, and health problems. Mounting evidence from functional neuroimaging and clinical studies implicates prefrontal-subcortical systems in processing financial information. This study examined the relationship of credit card debt and executive functions using the Frontal System Behavior Scale (FRSBE). After removing the influences of demographic variables (age, sex, education, and income), credit card debt was associated with the Executive Dysfunction scale, but not the Apathy or Disinhibition scales. This suggests that processes of conceptualizing and organizing finances are most relevant to credit card debt, and implicates dorsolateral prefrontal dysfunction.

Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults.

PubMed

Bäuml, Josef G; Daamen, Marcel; Meng, Chun; Neitzel, Julia; Scheef, Lukas; Jaekel, Julia; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Boecker, Henning; Wohlschläger, Afra M; Sorg, Christian

2015-11-01

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brain's large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Influence of the segmentation on the characterization of cerebral networks of structural damage for patients with disorders of consciousness

NASA Astrophysics Data System (ADS)

Martínez, Darwin; Mahalingam, Jamuna J.; Soddu, Andrea; Franco, Hugo; Lepore, Natasha; Laureys, Steven; Gómez, Francisco

2015-01-01

Disorders of consciousness (DOC) are a consequence of a variety of severe brain injuries. DOC commonly results in anatomical brain modifications, which can affect cortical and sub-cortical brain structures. Postmortem studies suggest that severity of brain damage correlates with level of impairment in DOC. In-vivo studies in neuroimaging mainly focus in alterations on single structures. Recent evidence suggests that rather than one, multiple brain regions can be simultaneously affected by this condition. In other words, DOC may be linked to an underlying cerebral network of structural damage. Recently, geometrical spatial relationships among key sub-cortical brain regions, such as left and right thalamus and brain stem, have been used for the characterization of this network. This approach is strongly supported on automatic segmentation processes, which aim to extract regions of interests without human intervention. Nevertheless, patients with DOC usually present massive structural brain changes. Therefore, segmentation methods may highly influence the characterization of the underlying cerebral network structure. In this work, we evaluate the level of characterization obtained by using the spatial relationships as descriptor of a sub-cortical cerebral network (left and right thalamus) in patients with DOC, when different segmentation approaches are used (FSL, Free-surfer and manual segmentation). Our results suggest that segmentation process may play a critical role for the construction of robust and reliable structural characterization of DOC conditions.

Stimulation Mapping of Myelinated Tracts in Awake Patients

PubMed Central

Duffau, Hugues

2016-01-01

For a long time, although the functional anatomy of human cortex has extensively been studied, subcortical white matter tracts have received little consideration. Recent advances in tractography have opened the door to a non-invasive investigation of the subcortical fibers in vivo. However, this method cannot study directly the function of the bundles. Interestingly, for the first time in the history of cognitive neurosciences, direct axonal electrostimulation (DES) mapping of the neural pathways offers the unique opportunity to investigate the function of the connectomal anatomy. Indeed, this technique is able to perform real-time anatomo-functional correlations in awake patients who undergo brain surgery, especially at the level of the subcortical fibers. Here, the aim is to review original data issued from DES of myelinated tracts in adults, with regard to the functional connectivity mediating the sensorimotor, visuo-spatial, language, cognitive and emotional functions, as well as the interactions between these different sub-networks, leading ultimately to explore consciousness. Therefore, axonal stimulation is a valuable tool in the field of connectomics, that is, the map of neural connections, in order to switch from the traditional localizationist view of brain processing to a networking model in which cerebral functions are underpinned by the dynamic interactions of large-scale distributed and parallel sub-circuits. Such connectomal account should integrate the anatomic constraint represented by the subcortical fascicles. Indeed, post-lesional neuroplasticity is possible only on the condition that the white matter fibers are preserved, to allow communication and temporal synchronization among delocalized inter-connected networks. PMID:29765851

Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia.

PubMed

Hainsworth, Atticus H; Minett, Thais; Andoh, Joycelyn; Forster, Gillian; Bhide, Ishaan; Barrick, Thomas R; Elderfield, Kay; Jeevahan, Jamuna; Markus, Hugh S; Bridges, Leslie R

2017-10-01

We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T 2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P =0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P =0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P =0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P =0.007). Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers. © 2017 American Heart Association, Inc.

Neurocognitive Dysfunction in Systemic Lupus Erythematosus: Association with Antiphospholipid Antibodies, Disease Activity and Chronic Damage

PubMed Central

Conti, Fabrizio; Alessandri, Cristiano; Perricone, Carlo; Scrivo, Rossana; Rezai, Soheila; Ceccarelli, Fulvia; Spinelli, Francesca Romana; Ortona, Elena; Marianetti, Massimo; Mina, Concetta; Valesini, Guido

2012-01-01

Introduction Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage. Methods Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5 antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and chronic damage. Patients were administered a test battery specifically designed to detect fronto-subcortical dysfunction across five domains: memory, attention, abstract reasoning, executive function and visuospatial function. For each patient, the raw scores from each test were compared with published norms, then transformed into Z scores (deviation from normal mean), and finally summed in the Global Cognitive Dysfunction score (GCDs). Results Nineteen percent of patients had mild GCDs impairment (GCDs 2–3), 7% moderate (GCDs 4–5) and 5% severe (GCDs≥6). The visuospatial domain was the most compromised (MDZs = −0.89±1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional and executive domains; SLICC correlated with GCDs, and with visuospatial and attentional domains impairment. Conclusions Anti-phospholipids, disease activity, and chronic damage are associated with cognitive dysfunction in SLE. The use of a wide spectrum of tests allowed for a better selection of the relevant factors involved in SLE cognitive dysfunction, and standardized neuropsychological testing methods should be used for routine assessment of SLE patients. PMID:22461897

Characterization of the Growth of Deep and Subcortical White Matter Hyperintensity on MR Imaging: A Retrospective Cohort Study.

PubMed

Adachi, Michito; Sato, Takamichi

2017-07-10

In elderly patients, deep and subcortical white matter hyperintense lesions are frequently observed on MRI; however, the growth process of these lesions is unclear. The aims of this retrospective cohort study were to elucidate the growth characteristics of deep and subcortical white matter hyperintense lesions, and to insight their etiology. We enrolled 103 patients (1610 lesions) whose deep and subcortical white matter hyperintense lesions were monitored for 3 or more years by MRI examination. The area of each hyperintense lesion was measured using a tracing method in the first and last MRI examinations. The annual rate of increase in the area of each lesion was calculated, and using the Pearson product-moment correlation coefficient the correlation between the annual rate of increase in area and the interval between the first and last MRI examinations was determined. The paired t-test showed a significant increase in the mean area of all the deep and subcortical white matter hyperintense lesions between the first and last MRI examinations (P < 0.001). However, hyperintense lesions had decreased in the area or disappeared in 227 (14.1%) lesions in the last MRI examination, particularly in patients with diabetes. The mean annual rate of increase in area of all hyperintense lesions was 0.013 ± 0.021 cm 2 per year. The annual rate of increase in area and the interval between the first and last MRI examinations showed a weak negative correlation (r = -0.121; P < 0.01). Decrease in the area and the disappearance of the subcortical white matter hyperintense lesions, and a decline in the annual rate of increase in the lesion area with time suggest that the interstitial fluid accumulation associated with dysfunctional drainage around the vessels may be involved in the possible etiologies of deep and subcortical white matter hyperintense lesions.

The nature of face representations in subcortical regions.

PubMed

Gabay, Shai; Burlingham, Charles; Behrmann, Marlene

2014-07-01

Studies examining the neural correlates of face perception in humans have focused almost exclusively on the distributed cortical network of face-selective regions. Recently, however, investigations have also identified subcortical correlates of face perception and the question addressed here concerns the nature of these subcortical face representations. To explore this issue, we presented to participants pairs of images sequentially to the same or to different eyes. Superior performance in the former over latter condition implicates monocular, prestriate portions of the visual system. Over a series of five experiments, we manipulated both lower-level (size, location) as well as higher-level (identity) similarity across the pair of faces. A monocular advantage was observed even when the faces in a pair differed in location and in size, implicating some subcortical invariance across lower-level image properties. A monocular advantage was also observed when the faces in a pair were two different images of the same individual, indicating the engagement of subcortical representations in more abstract, higher-level aspects of face processing. We conclude that subcortical structures of the visual system are involved, perhaps interactively, in multiple aspects of face perception, and not simply in deriving initial coarse representations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Connectomic markers of disease expression, genetic risk and resilience in bipolar disorder.

PubMed

Dima, D; Roberts, R E; Frangou, S

2016-01-05

Bipolar disorder (BD) is characterized by emotional dysregulation and cognitive deficits associated with abnormal connectivity between subcortical-primarily emotional processing regions-and prefrontal regulatory areas. Given the significant contribution of genetic factors to BD, studies in unaffected first-degree relatives can identify neural mechanisms of genetic risk but also resilience, thus paving the way for preventive interventions. Dynamic causal modeling (DCM) and random-effects Bayesian model selection were used to define and assess connectomic phenotypes linked to facial affect processing and working memory in a demographically matched sample of first-degree relatives carefully selected for resilience (n=25), euthymic patients with BD (n=41) and unrelated healthy controls (n=46). During facial affect processing, patients and relatives showed similarly increased frontolimbic connectivity; resilient relatives, however, evidenced additional adaptive hyperconnectivity within the ventral visual stream. During working memory processing, patients displayed widespread hypoconnectivity within the corresponding network. In contrast, working memory network connectivity in resilient relatives was comparable to that of controls. Our results indicate that frontolimbic dysfunction during affect processing could represent a marker of genetic risk to BD, and diffuse hypoconnectivity within the working memory network a marker of disease expression. The association of hyperconnectivity within the affect-processing network with resilience to BD suggests adaptive plasticity that allows for compensatory changes and encourages further investigation of this phenotype in genetic and early intervention studies.

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

PubMed Central

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients. PMID:29186356

Abulia following penetrating brain injury during endoscopic sinus surgery with disruption of the anterior cingulate circuit: case report.

PubMed

Grunsfeld, Alexander A; Login, Ivan S

2006-01-23

It is common knowledge that the frontal lobes mediate complex human behavior and that damage to these regions can cause executive dysfunction, apathy, disinhibition and personality changes. However, it is less well known that subcortical structures such as the caudate and thalamus are part of functionally segregated fronto-subcortical circuits, that can also alter behavior after injury. CASE PRESENTATION We present a 57 year old woman who suffered penetrating brain injury during endoscopic sinus surgery causing right basal ganglia injury which resulted in an abulic syndrome. Abulia does not result solely from cortical injury but can occur after disruption anywhere in the anterior cingulate circuit--in the case of our patient, most prominently at the right caudate.

Functional brain networks associated with cognitive control, cocaine dependence, and treatment outcome.

PubMed

Worhunsky, Patrick D; Stevens, Michael C; Carroll, Kathleen M; Rounsaville, Bruce J; Calhoun, Vince D; Pearlson, Godfrey D; Potenza, Marc N

2013-06-01

Individuals with cocaine dependence often evidence poor cognitive control. The purpose of this exploratory study was to investigate networks of functional connectivity underlying cognitive control in cocaine dependence and examine the relationship of the networks to the disorder and its treatment. Independent component analysis (ICA) was applied to fMRI data to investigate if regional activations underlying cognitive control processes operate in functional networks, and whether these networks relate to performance and treatment outcome measures in cocaine dependence. Twenty patients completed a Stroop task during fMRI prior to entering outpatient treatment and were compared to 20 control participants. ICA identified five distinct functional networks related to cognitive control interference events. Cocaine-dependent patients displayed differences in performance-related recruitment of three networks. Reduced involvement of a "top-down" fronto-cingular network contributing to conflict monitoring correlated with better treatment retention. Greater engagement of two "bottom-up" subcortical and ventral prefrontal networks related to cue-elicited motivational processing correlated with abstinence during treatment. The identification of subcortical networks linked to cocaine abstinence and cortical networks to treatment retention suggests that specific circuits may represent important, complementary targets in treatment development for cocaine dependence. 2013 APA, all rights reserved

Childhood adversity impacts on brain subcortical structures relevant to depression.

PubMed

Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J; Veltman, Dick J; Wittfeld, Katharina; van Erp, Theo G M; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Völzke, Henry; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian B; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J A; van Tol, Marie-Jose; Penninx, Brenda W J H; Thompson, Paul M; Hibar, Derrek P; Dannlowski, Udo; Grabe, Hans J

2017-03-01

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. Copyright © 2016. Published by Elsevier Ltd.

Connectivity constraints on cortical reorganization of neural circuits involved in object naming.

PubMed

Papagno, Costanza; Gallucci, Marcello; Casarotti, Alessandra; Castellano, Antonella; Falini, Andrea; Fava, Enrica; Giussani, Carlo; Carrabba, Giorgio; Bello, Lorenzo; Caramazza, Alfonso

2011-04-01

The brain's plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function. Copyright © 2011 Elsevier Inc. All rights reserved.

Leftward Bias of Visual Attention in Patients with End-Stage Renal Disease Receiving Dialysis: A Neglected Phenomenon.

PubMed

Mańkowska, Aleksandra; Heilman, Kenneth M; Williamson, John B; Biedunkiewicz, Bogdan; Dębska-Ślizień, Alicja; Harciarek, Michał

2017-12-01

Patients with end-stage renal disease (ESRD) who are receiving dialysis often have cognitive and behavioral changes, including impairments in sustained attention. Impairments in sustained attention appear to be the consequence of right hemisphere dysfunction. Right hemisphere brain networks are also important for the allocation of spatial attention. Therefore, the objective of this study was to learn whether patients with ESRD receiving dialysis might also have a spatial attentional bias. Eighteen nondemented patients with ESRD receiving dialysis but without any neurologic diseases (age range: 20 to 60 years) and 18 demographically matched healthy controls participated in this study. Participants performed a standard line bisection task using 24 horizontal lines (24 cm long and 2 mm thick) that were sequentially placed at eye level on a white board. Patients receiving dialysis had a significantly greater leftward bias than healthy controls. Patients with ESRD receiving dialysis appear to have an impaired ability to correctly allocate their spatial attention (spatial neglect). Although the reason for the patients' leftward bias needs to be elucidated, ESRD and/or dialysis may have induced right frontal-subcortical dysfunction that disinhibited the right parietal lobe, producing a left-sided attentional bias. Further studies are needed to test this hypothesis.

Effects of Stimulation of the Subthalamic Nucleus on Naming and Reading Nouns and Verbs in Parkinson's Disease

ERIC Educational Resources Information Center

Silveri, Maria Caterina; Ciccarelli, Nicoletta; Baldonero, Eleonora; Piano, Carla; Zinno, Massimiliano; Soleti, Francesco; Bentivoglio, Anna Rita; Albanese, Alberto; Daniele, Antonio

2012-01-01

An impairment for verbs has been described in patients with Parkinson's disease (PD), suggesting that a disruption of frontal-subcortical circuits may result in dysfunction of the neural systems involved in action-verb processing. A previous study suggested that deep brain stimulation (DBS) of the subthalamic nucleus (STN) during verb generation…

Monocular Advantage for Face Perception Implicates Subcortical Mechanisms in Adult Humans

PubMed Central

Gabay, Shai; Nestor, Adrian; Dundas, Eva; Behrmann, Marlene

2014-01-01

The ability to recognize faces accurately and rapidly is an evolutionarily adaptive process. Most studies examining the neural correlates of face perception in adult humans have focused on a distributed cortical network of face-selective regions. There is, however, robust evidence from phylogenetic and ontogenetic studies that implicates subcortical structures, and recently, some investigations in adult humans indicate subcortical correlates of face perception as well. The questions addressed here are whether low-level subcortical mechanisms for face perception (in the absence of changes in expression) are conserved in human adults, and if so, what is the nature of these subcortical representations. In a series of four experiments, we presented pairs of images to the same or different eyes. Participants’ performance demonstrated that subcortical mechanisms, indexed by monocular portions of the visual system, play a functional role in face perception. These mechanisms are sensitive to face-like configurations and afford a coarse representation of a face, comprised of primarily low spatial frequency information, which suffices for matching faces but not for more complex aspects of face perception such as sex differentiation. Importantly, these subcortical mechanisms are not implicated in the perception of other visual stimuli, such as cars or letter strings. These findings suggest a conservation of phylogenetically and ontogenetically lower-order systems in adult human face perception. The involvement of subcortical structures in face recognition provokes a reconsideration of current theories of face perception, which are reliant on cortical level processing, inasmuch as it bolsters the cross-species continuity of the biological system for face recognition. PMID:24236767

Abulia following penetrating brain injury during endoscopic sinus surgery with disruption of the anterior cingulate circuit: Case report

PubMed Central

Grunsfeld, Alexander A; Login, Ivan S

2006-01-01

Background It is common knowledge that the frontal lobes mediate complex human behavior and that damage to these regions can cause executive dysfunction, apathy, disinhibition and personality changes. However, it is less well known that subcortical structures such as the caudate and thalamus are part of functionally segregated fronto-subcortical circuits, that can also alter behavior after injury. Case presentation We present a 57 year old woman who suffered penetrating brain injury during endoscopic sinus surgery causing right basal ganglia injury which resulted in an abulic syndrome. Conclusion Abulia does not result solely from cortical injury but can occur after disruption anywhere in the anterior cingulate circuit – in the case of our patient, most prominently at the right caudate. PMID:16430769

Brainstem Correlates of Speech-in-Noise Perception in Children

PubMed Central

Anderson, Samira; Skoe, Erika; Chandrasekaran, Bharath; Zecker, Steven; Kraus, Nina

2010-01-01

Children often have difficulty understanding speech in challenging listening environments. In the absence of peripheral hearing loss, these speech perception difficulties may arise from dysfunction at more central levels in the auditory system, including subcortical structures. We examined brainstem encoding of pitch in a speech syllable in 38 school-age children. In children with poor speech-in-noise perception, we find impaired encoding of the fundamental frequency and the second harmonic, two important cues for pitch perception. Pitch, an important factor in speaker identification, aids the listener in tracking a specific voice from a background of voices. These results suggest that the robustness of subcortical neural encoding of pitch features in time-varying signals is an important factor in determining success with speech perception in noise. PMID:20708671

Beyond the Arcuate Fasciculus: Consensus and Controversy in the Connectional Anatomy of Language

ERIC Educational Resources Information Center

Dick, Anthony Steven; Tremblay, Pascale

2012-01-01

The growing consensus that language is distributed into large-scale cortical and subcortical networks has brought with it an increasing focus on the connectional anatomy of language, or how particular fibre pathways connect regions within the language network. Understanding connectivity of the language network could provide critical insights into…

Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

PubMed Central

Poggesi, Anna; Salvadori, Emilia; Pantoni, Leonardo; Pracucci, Giovanni; Cesari, Francesca; Chiti, Alberto; Ciolli, Laura; Cosottini, Mirco; Del Bene, Alessandra; De Stefano, Nicola; Diciotti, Stefano; Dotti, Maria Teresa; Ginestroni, Andrea; Giusti, Betti; Gori, Anna Maria; Nannucci, Serena; Orlandi, Giovanni; Pescini, Francesca; Valenti, Raffaella; Abbate, Rosanna; Federico, Antonio; Mascalchi, Mario; Murri, Luigi; Inzitari, Domenico

2012-01-01

Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD. PMID:22550606

Distinct Spatiotemporal Activation Patterns of the Perirhinal-Entorhinal Network in Response to Cortical and Amygdala Input

PubMed Central

Willems, Janske G. P.; Wadman, Wytse J.; Cappaert, Natalie L. M.

2016-01-01

The perirhinal (PER) and entorhinal cortex (EC) receive input from the agranular insular cortex (AiP) and the subcortical lateral amygdala (LA) and the main output area is the hippocampus. Information transfer through the PER/EC network however, is not always guaranteed. It is hypothesized that this network actively regulates the (sub)cortical activity transfer to the hippocampal network and that the inhibitory system is involved in this function. This study determined the recruitment by the AiP and LA afferents in PER/EC network with the use of voltage sensitive dye (VSD) imaging in horizontal mouse brain slices. Electrical stimulation (500 μA) of the AiP induced activity that gradually propagated predominantly in the rostro-caudal direction: from the PER to the lateral EC (LEC). In the presence of 1 μM of the competitive γ-aminobutyric acid (GABAA) receptor antagonist bicuculline, AiP stimulation recruited the medial EC (MEC) as well. In contrast, LA stimulation (500 μA) only induced activity in the deep layers of the PER. In the presence of bicuculline, the initial population activity in the PER propagated further towards the superficial layers and the EC after a delay. The latency of evoked responses decreased with increasing stimulus intensities (50–500 μA) for both the AiP and LA stimuli. The stimulation threshold for evoking responses in the PER/EC network was higher for the LA than for the AiP. This study showed that the extent of the PER/EC network activation depends on release of inhibition. When GABAA dependent inhibition is reduced, both the AiP and the LA activate spatially overlapping regions, although in a distinct spatiotemporal fashion. It is therefore hypothesized that the inhibitory network regulates excitatory activity from both cortical and subcortical areas that has to be transmitted through the PER/EC network. PMID:27378860

The Cerebral Cost of Breathing: An fMRI Case-Study in Congenital Central Hypoventilation Syndrome

PubMed Central

Sharman, Mike; Gallea, Cécile; Lehongre, Katia; Galanaud, Damien; Nicolas, Nathalie; Similowski, Thomas; Cohen, Laurent; Straus, Christian; Naccache, Lionel

2014-01-01

Certain motor activities - like walking or breathing - present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks - including various frontal lobe areas - subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the “resting state” pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active maintenance of cortical control over a continuous motor activity impacts on brain functioning and cognition. PMID:25268234

Transdiagnostic Associations Between Functional Brain Network Integrity and Cognition.

PubMed

Sheffield, Julia M; Kandala, Sridhar; Tamminga, Carol A; Pearlson, Godfrey D; Keshavan, Matcheri S; Sweeney, John A; Clementz, Brett A; Lerman-Sinkoff, Dov B; Hill, S Kristian; Barch, Deanna M

2017-06-01

Cognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs. To examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains. A total of 201 healthy control participants and 375 patients with psychotic disorders from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were studied from September 29, 2007, to May 31, 2011. The B-SNIP recruited healthy controls and stable outpatients from 6 sites: Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Detroit, Michigan; and Hartford, Connecticut. All participants underwent cognitive testing and resting-state functional magnetic resonance imaging. Data analysis was performed from April 28, 2015, to February 21, 2017. The Brief Assessment of Cognition in Schizophrenia was used to measure cognitive ability. A principal axis factor analysis on the Brief Assessment of Cognition in Schizophrenia battery yielded a single factor (54% variance explained) that served as the measure of general cognitive ability. Functional network integrity measures included global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network, and auditory network and exploratory analyses of all networks from the Power atlas. Group differences in network measures, associations between cognition and network measures, and mediation models were tested. The final sample for the current study included 201 healthy controls, 143 patients with schizophrenia, 103 patients with schizoaffective disorder, and 129 patients with psychotic bipolar disorder (mean [SD] age, 35.1 [12.0] years; 281 male [48.8%] and 295 female [51.2%]; 181 white [31.4%], 348 black [60.4%], and 47 other [8.2%]). Patients with schizophrenia (Cohen d = 0.36, P < .001) and psychotic bipolar disorder (Cohen d = 0.33, P = .002) had significantly reduced CON global efficiency compared with healthy controls. All patients with psychotic disorders had significantly reduced CON local efficiency, but the clinical groups did not differ from one another. The CON global efficiency was significantly associated with general cognitive ability across all groups (β = 0.099, P = .009) and significantly mediated the association between psychotic disorder status and general cognition (β = -0.037; 95% CI, -0.076 to -0.014). Subcortical network global efficiency was also significantly reduced in psychotic disorders (F3,587 = 4.01, P = .008) and positively predicted cognitive ability (β = 0.094, P = .009). These findings provide evidence that reduced CON and subcortical network efficiency play a role in the general cognitive deficit observed across the psychosis spectrum. They provide new support for the dimensional hypothesis that a shared neurobiological mechanism underlies cognitive impairment in psychotic disorders.

Alterations in working memory as a function of leukoaraiosis in dementia.

PubMed

Lamar, Melissa; Price, Catherine C; Libon, David J; Penney, Dana L; Kaplan, Edith; Grossman, Murray; Heilman, Kenneth M

2007-01-28

Dementia research suggests executive dysfunction is best understood within the context of disease-specific neuropathology. Leukoaraiosis (LA) results in executive dysfunction yet little is known about its impact on specific aspects of working memory (WM). This study aimed to investigate the relationship between MRI LA severity and WM in dementia. A visual rating scale was used to assign patients with dementia into groups with minimal-mild LA (Low LA; n=34) and moderate-severe LA (High LA; n=32). A modified Digit Span Backward Task consisting of 3-, 4-, and 5-span trials measured specific components of WM. Short-term storage and rehearsal in WM were assessed by the total number of digits reported regardless of recall order (ANY-ORDER; e.g., 47981 recalled '18943', score=4). Mental manipulation in the form of disengagement and temporal re-ordering was assessed by the total number of digits recalled in correct position (SERIAL-ORDER; e.g., 47981 recalled '18943', score=3). There was no difference between LA groups on ANY-ORDER comparisons. The High LA group obtained lower SERIAL-ORDER scores than the Low LA group. Stepwise regression analyses were conducted that first entered MMSE scores then composite z-scores reflecting executive functioning, language and memory. ANY-ORDER performance variance was explained solely by dementia severity. SERIAL-ORDER performance variance was further explained by executive dysfunction. Results suggest that high degrees of LA do not interfere with immediate (digit) recall but do interfere with disengagement and temporal re-ordering. LA may disconnect the frontal lobes from subcortical and cortical structures that form the neuronal networks critical for these WM functions.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Linking Essential Tremor to the Cerebellum: Physiological Evidence.

PubMed

Filip, Pavel; Lungu, Ovidiu V; Manto, Mario-Ubaldo; Bareš, Martin

2016-12-01

Essential tremor (ET), clinically characterized by postural and kinetic tremors, predominantly in the upper extremities, originates from pathological activity in the dynamic oscillatory network comprising the majority of nodes in the central motor network. Evidence indicates dysfunction in the thalamus, the olivocerebellar loops, and intermittent cortical engagement. Pathology of the cerebellum, a structure with architecture intrinsically predisposed to oscillatory activity, has also been implicated in ET as shown by clinical, neuroimaging, and pathological studies. Despite electrophysiological studies assessing cerebellar impairment in ET being scarce, their impact is tangible, as summarized in this review. The electromyography-magnetoencephalography combination provided the first direct evidence of pathological alteration in cortico-subcortical communication, with a significant emphasis on the cerebellum. Furthermore, complex electromyography studies showed disruptions in the timing of agonist and antagonist muscle activation, a process generally attributed to the cerebellum. Evidence pointing to cerebellar engagement in ET has also been found in electrooculography measurements, cerebellar repetitive transcranial magnetic stimulation studies, and, indirectly, in complex analyses of the activity of the ventral intermediate thalamic nucleus (an area primarily receiving inputs from the cerebellum), which is also used in the advanced treatment of ET. In summary, further progress in therapy will require comprehensive electrophysiological and physiological analyses to elucidate the precise mechanisms leading to disease symptoms. The cerebellum, as a major node of this dynamic oscillatory network, requires further study to aid this endeavor.

Interhemispheric Control of Unilateral Movement

PubMed Central

Beaulé, Vincent; Tremblay, Sara; Théoret, Hugo

2012-01-01

To perform strictly unilateral movements, the brain relies on a large cortical and subcortical network. This network enables healthy adults to perform complex unimanual motor tasks without the activation of contralateral muscles. However, mirror movements (involuntary movements in ipsilateral muscles that can accompany intended movement) can be seen in healthy individuals if a task is complex or fatiguing, in childhood, and with increasing age. Lateralization of movement depends on complex interhemispheric communication between cortical (i.e., dorsal premotor cortex, supplementary motor area) and subcortical (i.e., basal ganglia) areas, probably coursing through the corpus callosum (CC). Here, we will focus on transcallosal interhemispheric inhibition (IHI), which facilitates complex unilateral movements and appears to play an important role in handedness, pathological conditions such as Parkinson's disease, and stroke recovery. PMID:23304559

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia

PubMed Central

Kandiah, Nagaendran; Pai, Ming-Chyi; Senanarong, Vorapun; Looi, Irene; Ampil, Encarnita; Park, Kyung Won; Karanam, Ananda Krishna; Christopher, Stephen

2017-01-01

Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE−BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations. PMID:28458525

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson's disease dementia.

PubMed

Kandiah, Nagaendran; Pai, Ming-Chyi; Senanarong, Vorapun; Looi, Irene; Ampil, Encarnita; Park, Kyung Won; Karanam, Ananda Krishna; Christopher, Stephen

2017-01-01

Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.

Impulsivity and the Modular Organization of Resting-State Neural Networks

PubMed Central

Davis, F. Caroline; Knodt, Annchen R.; Sporns, Olaf; Lahey, Benjamin B.; Zald, David H.; Brigidi, Bart D.; Hariri, Ahmad R.

2013-01-01

Impulsivity is a complex trait associated with a range of maladaptive behaviors, including many forms of psychopathology. Previous research has implicated multiple neural circuits and neurotransmitter systems in impulsive behavior, but the relationship between impulsivity and organization of whole-brain networks has not yet been explored. Using graph theory analyses, we characterized the relationship between impulsivity and the functional segregation (“modularity”) of the whole-brain network architecture derived from resting-state functional magnetic resonance imaging (fMRI) data. These analyses revealed remarkable differences in network organization across the impulsivity spectrum. Specifically, in highly impulsive individuals, regulatory structures including medial and lateral regions of the prefrontal cortex were isolated from subcortical structures associated with appetitive drive, whereas these brain areas clustered together within the same module in less impulsive individuals. Further exploration of the modular organization of whole-brain networks revealed novel shifts in the functional connectivity between visual, sensorimotor, cortical, and subcortical structures across the impulsivity spectrum. The current findings highlight the utility of graph theory analyses of resting-state fMRI data in furthering our understanding of the neurobiological architecture of complex behaviors. PMID:22645253

Dorsolateral prefrontal cortex activation during emotional anticipation and neuropsychological performance in posttraumatic stress disorder.

PubMed

Aupperle, Robin L; Allard, Carolyn B; Grimes, Erin M; Simmons, Alan N; Flagan, Taru; Behrooznia, Michelle; Cissell, Shadha H; Twamley, Elizabeth W; Thorp, Steven R; Norman, Sonya B; Paulus, Martin P; Stein, Murray B

2012-04-01

Posttraumatic stress disorder (PTSD) has been associated with executive or attentional dysfunction and problems in emotion processing. However, it is unclear whether these two domains of dysfunction are related to common or distinct neurophysiological substrates. To examine the hypothesis that greater neuropsychological impairment in PTSD relates to greater disruption in prefrontal-subcortical networks during emotional anticipation. Case-control, cross-sectional study. General community and hospital and community psychiatric clinics. Volunteer sample of 37 women with PTSD related to intimate partner violence and 34 age-comparable healthy control women. We used functional magnetic resonance imaging (fMRI) to examine neural responses during anticipation of negative and positive emotional images. The Clinician-Administered PTSD Scale was used to characterize PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition, Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference Test, and Wisconsin Card Sorting Test were used to characterize neuropsychological performance. Women with PTSD performed worse on complex visuomotor processing speed (Digit Symbol Test) and executive function (Color-Word Interference Inhibition/Switching subtest) measures compared with control subjects. Posttraumatic stress disorder was associated with greater anterior insula and attenuated lateral prefrontal cortex (PFC) activation during emotional anticipation. Greater dorsolateral PFC activation (anticipation of negative images minus anticipation of positive images) was associated with lower PTSD symptom severity and better visuomotor processing speed and executive functioning. Greater medial PFC and amygdala activation related to slower visuomotor processing speed. During emotional anticipation, women with PTSD show exaggerated activation in the anterior insula, a region important for monitoring internal bodily state. Greater dorsolateral PFC response in PTSD patients during emotional anticipation may reflect engagement of cognitive control networks that are beneficial for emotional and cognitive functioning. Novel treatments could be aimed at strengthening the balance between cognitive control (dorsolateral PFC) and affective processing (medial PFC and amygdala) networks to improve overall functioning for PTSD patients.

Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

PubMed Central

Wagshal, Dana; Knowlton, Barbara Jean; Cohen, Jessica Rachel; Bookheimer, Susan Yost; Bilder, Robert Martin; Fernandez, Vindia Gisela; Asarnow, Robert Franklin

2015-01-01

Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia. PMID:25541139

Frequency and Predictors of Dysphagia in Patients With Recent Small Subcortical Infarcts.

PubMed

Fandler, Simon; Gattringer, Thomas; Eppinger, Sebastian; Doppelhofer, Kathrin; Pinter, Daniela; Niederkorn, Kurt; Enzinger, Christian; Wardlaw, Joanna M; Fazekas, Franz

2017-01-01

Detailed data on the occurrence of swallowing dysfunction in patients with recent small subcortical infarcts (RSSI) in the context of cerebral small vessel disease are lacking. This prompted us to assess the frequency of and risk factors for dysphagia in RSSI patients. We identified all inpatients with magnetic resonance imaging-confirmed RSSI between January 2008 and February 2013. Demographic and clinical data were extracted from our stroke database, and magnetic resonance imaging scans were reviewed for morphological changes. Dysphagia was determined according to the Gugging Swallowing Screen. We identified 332 patients with RSSI (mean age, 67.7±11.9 years; 64.5% male). Overall, 83 patients (25%) had dysphagia, which was mild in 46 (55.4%), moderate in 26 (31.3%), and severe in 11 patients (13.3%). The rate of dysphagia in patients with supratentorial RSSI was 20%. Multivariate analysis identified a higher National Institutes of Health Stroke Scale score (P<0.001), pontine infarction (P<0.01), and more severe white matter hyperintensities (Fazekas grades 2 and 3, P=0.03) as risk factors for swallowing dysfunction. Dysphagia is present in a quarter of patients with RSSI and has to be expected especially in those with higher stroke severity, pontine infarction, and severe white matter hyperintensities. © 2016 American Heart Association, Inc.

Differences between child and adult large-scale functional brain networks for reading tasks.

PubMed

Liu, Xin; Gao, Yue; Di, Qiqi; Hu, Jiali; Lu, Chunming; Nan, Yun; Booth, James R; Liu, Li

2018-02-01

Reading is an important high-level cognitive function of the human brain, requiring interaction among multiple brain regions. Revealing differences between children's large-scale functional brain networks for reading tasks and those of adults helps us to understand how the functional network changes over reading development. Here we used functional magnetic resonance imaging data of 17 adults (19-28 years old) and 16 children (11-13 years old), and graph theoretical analyses to investigate age-related changes in large-scale functional networks during rhyming and meaning judgment tasks on pairs of visually presented Chinese characters. We found that: (1) adults had stronger inter-regional connectivity and nodal degree in occipital regions, while children had stronger inter-regional connectivity in temporal regions, suggesting that adults rely more on visual orthographic processing whereas children rely more on auditory phonological processing during reading. (2) Only adults showed between-task differences in inter-regional connectivity and nodal degree, whereas children showed no task differences, suggesting the topological organization of adults' reading network is more specialized. (3) Children showed greater inter-regional connectivity and nodal degree than adults in multiple subcortical regions; the hubs in children were more distributed in subcortical regions while the hubs in adults were more distributed in cortical regions. These findings suggest that reading development is manifested by a shift from reliance on subcortical to cortical regions. Taken together, our study suggests that Chinese reading development is supported by developmental changes in brain connectivity properties, and some of these changes may be domain-general while others may be specific to the reading domain. © 2017 Wiley Periodicals, Inc.

Post-stroke dementia: the contribution of thalamus and basal ganglia changes.

PubMed

Lopes, Marcos Antonio; Firbank, Michael J; Widdrington, Michelle; Blamire, Andrew M; Kalaria, Raj N; O'Brien, John T

2012-04-01

The neurobiological basis of increased risk of dementia in stroke patients is unclear, though there are several related pathological changes, including white matter hyperintensities (WMH), and medial temporal atrophy. Subcortical gray matter structures have also been implicated in dementia resulting from vascular pathology, particularly vascular dementia. This study aimed to investigate the contribution of changes in subcortical gray matter structures to post-stroke dementia (PSD). T1- and T2-weighted images and T2-weighted fluid-attenuated inversion recovery (FLAIR) images were obtained on a 3-Tesla magnetic resonance (MR) system, in four groups aged over 75 years: post-stroke with dementia (PSD; 8), post-stroke no dementia (PSnoD; 33), Alzheimer's disease (AD; 26) and controls (30). Automated software was used to measure the volume of thalamus, putamen, caudate nucleus, and hippocampus as well as total WMH volume. The number of subcortical lacunes was also counted. The number of caudate lacunes was higher in the PSnoD group, compared with AD (p = 0.029) and controls (p = 0.019). The putamen volume was smaller in the stroke and AD groups, when compared with controls. In the whole stroke group, putamen lacunes were correlated with impairment in memory (Rey test; ρ = -0.365; p = 0.031), while WMH and hippocampal volume both correlated with global dysfunction. Our findings implicate a variety of neurobiological substrates of dementia, such as small vessel disease and Alzheimer pathology, which develop after stroke in an old older population, with a contribution from subcortical brain structures.

Cocaine dependence and thalamic functional connectivity: a multivariate pattern analysis.

PubMed

Zhang, Sheng; Hu, Sien; Sinha, Rajita; Potenza, Marc N; Malison, Robert T; Li, Chiang-Shan R

2016-01-01

Cocaine dependence is associated with deficits in cognitive control. Previous studies demonstrated that chronic cocaine use affects the activity and functional connectivity of the thalamus, a subcortical structure critical for cognitive functioning. However, the thalamus contains nuclei heterogeneous in functions, and it is not known how thalamic subregions contribute to cognitive dysfunctions in cocaine dependence. To address this issue, we used multivariate pattern analysis (MVPA) to examine how functional connectivity of the thalamus distinguishes 100 cocaine-dependent participants (CD) from 100 demographically matched healthy control individuals (HC). We characterized six task-related networks with independent component analysis of fMRI data of a stop signal task and employed MVPA to distinguish CD from HC on the basis of voxel-wise thalamic connectivity to the six independent components. In an unbiased model of distinct training and testing data, the analysis correctly classified 72% of subjects with leave-one-out cross-validation (p < 0.001), superior to comparison brain regions with similar voxel counts (p < 0.004, two-sample t test). Thalamic voxels that form the basis of classification aggregate in distinct subclusters, suggesting that connectivities of thalamic subnuclei distinguish CD from HC. Further, linear regressions provided suggestive evidence for a correlation of the thalamic connectivities with clinical variables and performance measures on the stop signal task. Together, these findings support thalamic circuit dysfunction in cognitive control as an important neural marker of cocaine dependence.

An unbiased Bayesian approach to functional connectomics implicates social-communication networks in autism

PubMed Central

Venkataraman, Archana; Duncan, James S.; Yang, Daniel Y.-J.; Pelphrey, Kevin A.

2015-01-01

Resting-state functional magnetic resonance imaging (rsfMRI) studies reveal a complex pattern of hyper- and hypo-connectivity in children with autism spectrum disorder (ASD). Whereas rsfMRI findings tend to implicate the default mode network and subcortical areas in ASD, task fMRI and behavioral experiments point to social dysfunction as a unifying impairment of the disorder. Here, we leverage a novel Bayesian framework for whole-brain functional connectomics that aggregates population differences in connectivity to localize a subset of foci that are most affected by ASD. Our approach is entirely data-driven and does not impose spatial constraints on the region foci or dictate the trajectory of altered functional pathways. We apply our method to data from the openly shared Autism Brain Imaging Data Exchange (ABIDE) and pinpoint two intrinsic functional networks that distinguish ASD patients from typically developing controls. One network involves foci in the right temporal pole, left posterior cingulate cortex, left supramarginal gyrus, and left middle temporal gyrus. Automated decoding of this network by the Neurosynth meta-analytic database suggests high-level concepts of “language” and “comprehension” as the likely functional correlates. The second network consists of the left banks of the superior temporal sulcus, right posterior superior temporal sulcus extending into temporo-parietal junction, and right middle temporal gyrus. Associated functionality of these regions includes “social” and “person”. The abnormal pathways emanating from the above foci indicate that ASD patients simultaneously exhibit reduced long-range or inter-hemispheric connectivity and increased short-range or intra-hemispheric connectivity. Our findings reveal new insights into ASD and highlight possible neural mechanisms of the disorder. PMID:26106561

A Network Model of the Emotional Brain.

PubMed

Pessoa, Luiz

2017-05-01

Emotion is often understood in terms of a circumscribed set of cortical and subcortical brain regions. I propose, instead, that emotion should be understood in terms of large-scale network interactions spanning the entire neuroaxis. I describe multiple anatomical and functional principles of brain organization that lead to the concept of 'functionally integrated systems', cortical-subcortical systems that anchor the organization of emotion in the brain. The proposal is illustrated by describing the cortex-amygdala integrated system and how it intersects with systems involving the ventral striatum/accumbens, septum, hippocampus, hypothalamus, and brainstem. The important role of the thalamus is also highlighted. Overall, the model clarifies why the impact of emotion is wide-ranging, and how emotion is interlocked with perception, cognition, motivation, and action. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disentangling interoception: insights from focal strokes affecting the perception of external and internal milieus

PubMed Central

Couto, Blas; Adolfi, Federico; Sedeño, Lucas; Salles, Alejo; Canales-Johnson, Andrés; Alvarez-Abut, Pablo; Garcia-Cordero, Indira; Pietto, Marcos; Bekinschtein, Tristan; Sigman, Mariano; Manes, Facundo; Ibanez, Agustin

2015-01-01

Interoception is the moment-to-moment sensing of the physiological condition of the body. The multimodal sources of interoception can be classified into two different streams of afferents: an internal pathway of signals arising from core structures (i.e., heart, blood vessels, and bronchi) and an external pathway of body-mapped sensations (i.e., chemosensation and pain) arising from peripersonal space. This study examines differential processing along these streams within the insular cortex (IC) and their subcortical tracts connecting frontotemporal networks. Two rare patients presenting focal lesions of the IC (insular lesion, IL) or its subcortical tracts (subcortical lesion, SL) were tested. Internally generated interoceptive streams were assessed through a heartbeat detection (HBD) task, while those externally triggered were tapped via taste, smell, and pain recognition tasks. A differential pattern was observed. The IC patient showed impaired internal signal processing while the SL patient exhibited external perception deficits. Such selective deficits remained even when comparing each patient with a group of healthy controls and a group of brain-damaged patients. These outcomes suggest the existence of distinguishable interoceptive streams. Results are discussed in relation with neuroanatomical substrates, involving a fronto-insulo-temporal network for interoceptive and cognitive contextual integration. PMID:25983697

A re-examination of neural basis of language processing: proposal of a dynamic hodotopical model from data provided by brain stimulation mapping during picture naming.

PubMed

Duffau, Hugues; Moritz-Gasser, Sylvie; Mandonnet, Emmanuel

2014-04-01

From recent findings provided by brain stimulation mapping during picture naming, we re-examine the neural basis of language. We studied structural-functional relationships by correlating the types of language disturbances generated by stimulation in awake patients, mimicking a transient virtual lesion both at cortical and subcortical levels (white matter and deep grey nuclei), with the anatomical location of the stimulation probe. We propose a hodotopical (delocalized) and dynamic model of language processing, which challenges the traditional modular and serial view. According to this model, following the visual input, the language network is organized in parallel, segregated (even if interconnected) large-scale cortico-subcortical sub-networks underlying semantic, phonological and syntactic processing. Our model offers several advantages (i) it explains double dissociations during stimulation (comprehension versus naming disorders, semantic versus phonemic paraphasias, syntactic versus naming disturbances, plurimodal judgment versus naming disorders); (ii) it takes into account the cortical and subcortical anatomic constraints; (iii) it explains the possible recovery of aphasia following a lesion within the "classical" language areas; (iv) it establishes links with a model executive functions. Copyright © 2013 Elsevier Inc. All rights reserved.

Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank

PubMed Central

Reus, L. M.; Shen, X.; Gibson, J.; Wigmore, E.; Ligthart, L.; Adams, M. J.; Davies, G.; Cox, S. R.; Hagenaars, S. P.; Bastin, M. E.; Deary, I. J.; Whalley, H. C.; McIntosh, A. M.

2017-01-01

Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data comprised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). The calculation of polygenic risk scores was based on genome-wide association study results generated by the Psychiatric Genomics Consortium. Our findings indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders. PMID:28186152

Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank.

PubMed

Reus, L M; Shen, X; Gibson, J; Wigmore, E; Ligthart, L; Adams, M J; Davies, G; Cox, S R; Hagenaars, S P; Bastin, M E; Deary, I J; Whalley, H C; McIntosh, A M

2017-02-10

Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data comprised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). The calculation of polygenic risk scores was based on genome-wide association study results generated by the Psychiatric Genomics Consortium. Our findings indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders.

Theoretical Exploration of the Neural Bases of Behavioural Disinhibition, Apathy and Executive Dysfunction in Preclinical Alzheimer's Disease in People with Down's Syndrome: Potential Involvement of Multiple Frontal-Subcortical Neuronal Circuits

ERIC Educational Resources Information Center

Ball, S. L.; Holland, A. J.; Watson, P. C.; Huppert, F. A.

2010-01-01

Background: Recent research has suggested a specific impairment in frontal-lobe functioning in the preclinical stages of Alzheimer's disease (AD) in people with Down's syndrome (DS), characterised by prominent changes in personality or behaviour. The aim of the current paper is to explore whether particular kinds of change (namely executive…

In vivo Visuotopic Brain Mapping with Manganese-Enhanced MRI and Resting-State Functional Connectivity MRI

PubMed Central

Chan, Kevin C.; Fan, Shu-Juan; Chan, Russell W.; Cheng, Joe S.; Zhou, Iris Y.; Wu, Ed X.

2014-01-01

The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn2+ administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural-functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn2+ injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn2+ transfer but not intra- or inter-hemispheric monosynaptic Mn2+ transport after Mn2+ injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the neuroarchitecture, neurophysiology and structural-functional relationships of the visual brains in vivo. These may possess great potentials for effective monitoring and understanding of the basic anatomical and functional connections in the visual system during development, plasticity, disease, pharmacological interventions and genetic modifications in future studies. PMID:24394694

Double dissociation between syntactic gender and picture naming processing: a brain stimulation mapping study.

PubMed

Vidorreta, Jose Garbizu; Garcia, Roser; Moritz-Gasser, Sylvie; Duffau, Hugues

2011-03-01

Neural foundations of syntactic gender processing remain poorly understood. We used electrostimulation mapping in nine right-handed awake patients during surgery for a glioma within the left hemisphere, to study whether the cortico-subcortical structures involved in naming versus syntactic gender processing are common or distinct. In French, the article determines the grammatical gender. Thus, the patient was asked to perform a picture naming task and to give the appropriate article for each picture, with and without stimulation. Cortical stimulation elicited reproducible syntactic gender disturbances in six patients, in the inferior frontal gyrus (three cases), and in the posterior middle temporal gyrus (three cases). Interestingly, no naming disorders were generated during stimulation of the syntactic sites, while cortical areas inducing naming disturbances never elicited grammatical gender errors when stimulated. Moreover, at the subcortical level, stimulation of the white matter lateral to the caudate nucleus induced gender errors in three patients, with no naming disorders. Using cortico-subcortical electrical mapping in awake patients, we demonstrate for the first time (1) a double dissociation between syntactic gender and naming processing, supporting independent network model rather than serial theory, (2) the involvement of the left inferior frontal gyrus, especially the pars triangularis, and the posterior left middle temporal gyrus in grammatical gender processing, (3) the existence of white matter pathways, likely a sub-part of the left superior longitudinal fasciculus, underlying a large-scale distributed cortico-subcortical circuit which might selectively sub-serve syntactic gender processing, even if interconnected with parallel sub-networks involved in naming (semantic and phonological) processing. Copyright © 2010 Wiley-Liss, Inc.

Decreased Functional Brain Connectivity in Adolescents with Internet Addiction

PubMed Central

Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

2013-01-01

Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology. PMID:23451272

Repetitive transcranial magnetic stimulation induced modulations of resting state motor connectivity in writer's cramp.

PubMed

Bharath, R D; Biswal, B B; Bhaskar, M V; Gohel, S; Jhunjhunwala, K; Panda, R; George, L; Gupta, A K; Pal, P K

2015-05-01

Writer's cramp (WC) is a focal task-specific dystonia of the hand which is increasingly being accepted as a network disorder. Non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsfMRI). Nineteen patients with right-sided WC and 20 matched healthy controls (HCs) were prospectively evaluated. All patients underwent a single session of rTMS and rsfMRI was acquired before (R1) and after (R2) rTMS. Seed-based functional connectivity analysis of several regions in the motor network was performed for HCs, R1 and R2 using SPM8 software. Thresholded (P < 0.05, false discovery rate corrected) group level mean correlation maps were used to derive significantly connected region of interest pairs. Writer's cramp showed a significant reduction in resting state functional connectivity in comparison with HCs involving the left cerebellum, thalamus, globus pallidus, putamen, bilateral supplementary motor area, right medial prefrontal lobe and right post central gyrus. After rTMS there was a significant increase in the contralateral resting state functional connectivity through the left thalamus-right globus pallidus-right thalamus-right prefrontal lobe network loop. It is concluded that WC is a network disorder with widespread dysfunction much larger than clinically evident and changes induced by rTMS probably act through subcortical and trans-hemispheric unaffected connections. Longitudinal studies with therapeutic rTMS will be required to ascertain whether such information could be used to select patients prior to rTMS therapy. © 2015 EAN.

Principles and management of neuropsychiatric symptoms in Alzheimer's dementia.

PubMed

Nowrangi, Milap A; Lyketsos, Constantine G; Rosenberg, Paul B

2015-01-29

Neuropsychiatric symptoms of Alzheimer's disease (NPS-AD) are highly prevalent and lead to poor medical and functional outcomes. In spite of the burdensome nature of NPS-AD, we are continuing to refine the nosology and only beginning to understand the underlying pathophysiology. Cluster analyses have frequently identified three to five subsyndromes of NPS-AD: behavioral dysfunction (for example, agitation/aggressiveness), psychosis (for example, delusions and hallucinations), and mood disturbance (for example, depression or apathy). Recent neurobiological studies have used new neuroimaging techniques to elucidate behaviorally relevant circuits and networks associated with these subsyndromes. Several fronto-subcortical circuits, cortico-cortical networks, and neurotransmitter systems have been proposed as regions and mechanisms underlying NPS-AD. Common to most of these subsyndromes is the broad overlap of regions associated with the salience network (anterior cingulate and insula), mood regulation (amygdala), and motivated behavior (frontal cortex). Treatment strategies for dysregulated mood syndromes (depression and apathy) have primarily targeted serotonergic mechanisms with antidepressants or dopaminergic mechanisms with psychostimulants. Psychotic symptoms have largely been targeted with anti-psychotic medications despite controversial risk/benefit tradeoffs. Management of behavioral dyscontrol, including agitation and aggression in AD, has encompassed a wide range of psychoactive medications as well as non-pharmacological approaches. Developing rational therapeutic approaches for NPS-AD will require a firmer understanding of the underlying etiology in order to improve nosology as well as provide the empirical evidence necessary to overcome regulatory and funding challenges to further study these debilitating symptoms.

Subcortical brain atrophy in Gulf War Illness.

PubMed

Christova, Peka; James, Lisa M; Engdahl, Brian E; Lewis, Scott M; Carpenter, Adam F; Georgopoulos, Apostolos P

2017-09-01

Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-1991 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. Although brain dysfunction in GWI has been well documented (EBioMedicine 12:127-32, 2016), abnormalities in brain structure have been debated. Here we report a substantial (~10%) subcortical brain atrophy in GWI comprising mainly the brainstem, cerebellum and thalamus, and, to a lesser extent, basal ganglia, amygdala and diencephalon. The highest atrophy was observed in the brainstem, followed by left cerebellum and right thalamus, then by right cerebellum and left thalamus. These findings indicate graded atrophy of regions anatomically connected through the brainstem via the crossed superior cerebellar peduncle (left cerebellum → right thalamus, right cerebellum → left thalamus). This distribution of atrophy, together with the observed systematic reduction in volume of other subcortical areas (basal ganglia, amygdala and diencephalon), resemble the distribution of atrophy seen in toxic encephalopathy (Am J Neuroradiol 13:747-760, 1992) caused by a variety of substances, including organic solvents. Given the potential exposure of Gulf War veterans to "a wide range of biological and chemical agents including sand, smoke from oil-well fires, paints, solvents, insecticides, petroleum fuels and their combustion products, organophosphate nerve agents, pyridostigmine bromide, …" (Institute of Medicine National Research Council. Gulf War and Health: Volume 1. Depleted uranium, pyridostigmine bromide, sarin, and vaccines. National Academies Press, Washington DC, 2000), it is reasonable to suppose that such exposures, alone or in combination, could underlie the subcortical atrophy observed.

Mental steps: Differential activation of internal pacemakers in motor imagery and in mental imitation of gait.

PubMed

Sacheli, Lucia Maria; Zapparoli, Laura; De Santis, Carlo; Preti, Matteo; Pelosi, Catia; Ursino, Nicola; Zerbi, Alberto; Banfi, Giuseppe; Paulesu, Eraldo

2017-10-01

Gait imagery and gait observation can boost the recovery of locomotion dysfunctions; yet, a neurologically justified rationale for their clinical application is lacking as much as a direct comparison of their neural correlates. Using functional magnetic resonance imaging, we measured the neural correlates of explicit motor imagery of gait during observation of in-motion videos shot in a park with a steady cam (Virtual Walking task). In a 2 × 2 factorial design, we assessed the modulatory effect of gait observation and of foot movement execution on the neural correlates of the Virtual Walking task: in half of the trials, the participants were asked to mentally imitate a human model shown while walking along the same route (mental imitation condition); moreover, for half of all the trials, the participants also performed rhythmic ankle dorsiflexion as a proxy for stepping movements. We found that, beyond the areas associated with the execution of lower limb movements (the paracentral lobule, the supplementary motor area, and the cerebellum), gait imagery also recruited dorsal premotor and posterior parietal areas known to contribute to the adaptation of walking patterns to environmental cues. When compared with mental imitation, motor imagery recruited a more extensive network, including a brainstem area compatible with the human mesencephalic locomotor region (MLR). Reduced activation of the MLR in mental imitation indicates that this more visually guided task poses less demand on subcortical structures crucial for internally generated gait patterns. This finding may explain why patients with subcortical degeneration benefit from rehabilitation protocols based on gait observation. Hum Brain Mapp 38:5195-5216, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Divergent structural brain abnormalities between different genetic subtypes of children with Prader-Willi syndrome.

PubMed

Lukoshe, Akvile; White, Tonya; Schmidt, Marcus N; van der Lugt, Aad; Hokken-Koelega, Anita C

2013-10-22

Prader-Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD.

Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

PubMed Central

2013-01-01

Background Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. Methods High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. Results Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. Conclusions Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD. PMID:24144356

Current management of the cognitive dysfunction in Parkinson's disease: how far have we come?

PubMed

Vale, Salvador

2008-08-01

Parkinson's disease (PD) clinical features comprise both motor and nonmotor manifestations. Among the nonmotor complications, dementia is the most important. Approximately 40% of PD patients are affected by cognitive impairment. Remarkably, in addition to age, dementia is an independent predictor of mortality, whereas age at onset of PD and severity of neurological symptoms are not. In this review, I summarize the current knowledge of the pathogenesis of the PD cognitive impairment in relation to the therapies presently accessible and those that could become strategic in the near future. It is hypothesized that patients with PD show two components of cognitive dysfunction (CD): a generalized profile of subcortical dementia (PDsCD), and an overlapped pattern suggesting specific prefrontal damage with CD (PDpFCD). PDsCD is associated with structural neocortical/subcortical changes in the brain (in frontal, parietal, limbic, and temporal lobes, as well as in midbrain structures). In PDpFCD cognitive deficits comprise impairments in neuropsychological tests sensitive for frontal lobe function (discrete elements of episodic and working memory for instance), which are considered to be the consequence of dysfunction in neuronal loops connecting the prefrontal cortex and basal ganglia. Drugs reviewed for targeting PDsCD include: cholinesterase inhibitors, agents with mixed cholinergic and dopaminergic properties, antiglutamatergic drugs, mixed antiglutamatergic/dopaminergic agents; antioxidants and enhancers of mitochondrial functions, and anti-COX-2, as well as other anti-inflammatory mediators. Preliminary studies with vehicles that may target PDpFCD include piribedil, tolcapone, amantadine, and farampator. Additional agents (citicoline and neuroimmuniphilines, among others) will be outlined. A brief overview on neuroprotection and promising new biological advances in PD (deep brain stimulation, stem cells, gene therapy) also will be summarized.

Common genetic variants influence human subcortical brain structures.

PubMed

Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

2015-04-09

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Subcortical encoding of speech cues in children with attention deficit hyperactivity disorder.

PubMed

Jafari, Zahra; Malayeri, Saeed; Rostami, Reza

2015-02-01

There is little information about processing of nonspeech and speech stimuli at the subcortical level in individuals with attention deficit hyperactivity disorder (ADHD). The auditory brainstem response (ABR) provides information about the function of the auditory brainstem pathways. We aim to investigate the subcortical function in neural encoding of click and speech stimuli in children with ADHD. The subjects include 50 children with ADHD and 34 typically developing (TD) children between the ages of 8 and 12 years. Click ABR (cABR) and speech ABR (sABR) with 40 ms synthetic /da/ syllable stimulus were recorded. Latencies of cABR in waves of III and V and duration of V-Vn (P⩽0.027), and latencies of sABR in waves A, D, E, F and O and duration of V-A (P⩽0.034) were significantly longer in children with ADHD than in TD children. There were no apparent differences in components the sustained frequency following response (FFR). We conclude that children with ADHD have deficits in temporal neural encoding of both nonspeech and speech stimuli. There is a common dysfunction in the processing of click and speech stimuli at the brainstem level in children with suspected ADHD. Copyright © 2015. Published by Elsevier Ireland Ltd.

Subcortical Control of Precision Grip after Human Spinal Cord Injury

PubMed Central

Bunday, Karen L.; Tazoe, Toshiki; Rothwell, John C.

2014-01-01

The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients. Regardless of whether cortical and cervicomedullary stimulation was used, suppression of the MEP was only evident 1–3 ms after its onset. Long-term (∼5 years) use of the GABAb receptor agonist baclofen by SCI patients reduced MEP size during precision grip to similar levels as uninjured humans. Index finger sensory function correlated with MEP size during precision grip in SCI patients. Intracortical inhibition decreased during precision grip and spinal motoneuron excitability remained unchanged in all groups. Our results demonstrate that the control of precision grip in humans involves premotoneuronal subcortical mechanisms, likely disynaptic or polysynaptic spinal pathways that are lacking after SCI and restored by long-term use of baclofen. We propose that spinal GABAb-ergic interneuronal circuits, which are sensitive to baclofen, are part of the subcortical premotoneuronal network shaping corticospinal output during human precision grip. PMID:24849366

[The clinical phenomenology of Rett's syndrome].

PubMed

Calderón-González, R; Calderón-Sepulveda, R F; Treviño-Welsh, J

1999-01-01

The work was done to facilitate the clinical diagnosis and understanding of Rett syndrome (RS) by grouping the symptoms and signs in areas of neurological disfunction. This is a retrospective, longitudinal and observational study of 30 young females whose clinical manifestations were grouped using a modified Fitzgerald et al. scale for motor and behavior evaluation of patients with RS. All patients were videotaped at least during one or several appointments during their follow-up for a period of 1 to 10 years. All patients and videotapes were reviewed independently by the three authors. We followed the clinical diagnostic criteria of classic RS, and grouped the symptoms and signs in 12 groups of clinical phenomenology that represented specific areas of central or peripheral nervous system involvement: 1) dementia syndrome (fronto-temporo-parietal and limbic dysfunction); 2) extrapyramidal syndrome (basal ganglia dysfunction); 3) respiratory function disorders (brain stem reticular system disfunction); 4) sleep disorders (reticular system and limbic dysfunction); 5) epilepsy (cortico-subcortical paroxysmal bioelectrical dysfunction); 6) lower motor neuron syndrome (neuropathic dysfunction and/or peripheral neuropathy); 7) body growth retardation; 8) tonic-postural skeletal deformities; 9) deficit of pain sensation (nociceptive deficit); 10) pseudobulbar dysfunction; 11) autonomic dysfunction and 12) others (microcephaly and bruxism). In clinical practice, we recommend the use of this grouping of symptoms and signs because it makes facilities the clinical study, definition of areas of dysfunction and diagnosis of the patient with RS.

Technical principles of direct bipolar electrostimulation for cortical and subcortical mapping in awake craniotomy.

PubMed

Pallud, J; Mandonnet, E; Corns, R; Dezamis, E; Parraga, E; Zanello, M; Spena, G

2017-06-01

Intraoperative application of electrical current to the brain is a standard technique during brain surgery for inferring the function of the underlying brain. The purpose of intraoperative functional mapping is to reliably identify cortical areas and subcortical pathways involved in eloquent functions, especially motor, sensory, language and cognitive functions. The aim of this article is to review the rationale and the electrophysiological principles of the use of direct bipolar electrostimulation for cortical and subcortical mapping under awake conditions. Direct electrical stimulation is a window into the whole functional network that sustains a particular function. It is an accurate (spatial resolution of about 5mm) and a reproducible technique particularly adapted to clinical practice for brain resection in eloquent areas. If the procedure is rigorously applied, the sensitivity of direct electrical stimulation for the detection of cortical and subcortical eloquent areas is nearly 100%. The main disadvantage of this technique is its suboptimal specificity. Another limitation is the identification of eloquent areas during surgery, which, however, could have been functionally compensated postoperatively if removed surgically. Direct electrical stimulation is an easy, accurate, reliable and safe invasive technique for the intraoperative detection of both cortical and subcortical functional brain connectivity for clinical purpose. In our opinion, it is the optimal technique for minimizing the risk of neurological sequelae when resecting in eloquent brain areas. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Learning temporal statistics for sensory predictions in mild cognitive impairment.

PubMed

Di Bernardi Luft, Caroline; Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

2015-08-01

Training is known to improve performance in a variety of perceptual and cognitive skills. However, there is accumulating evidence that mere exposure (i.e. without supervised training) to regularities (i.e. patterns that co-occur in the environment) facilitates our ability to learn contingencies that allow us to interpret the current scene and make predictions about future events. Recent neuroimaging studies have implicated fronto-striatal and medial temporal lobe brain regions in the learning of spatial and temporal statistics. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are characterized by hippocampal dysfunction are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards orientated gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. However, our fMRI results demonstrate that MCI-AD patients recruit an alternate circuit to hippocampus to succeed in learning of predictive structures. In particular, we observed stronger learning-dependent activations for structured sequences in frontal, subcortical and cerebellar regions for patients compared to age-matched controls. Thus, our findings suggest a cortico-striatal-cerebellar network that may mediate the ability for predictive learning despite hippocampal dysfunction in MCI-AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Language experience differentiates prefrontal and subcortical activation of the cognitive control network in novel word learning

PubMed Central

King, Kelly E.; Hernandez, Arturo E.

2012-01-01

The purpose of this study was to examine the cognitive control mechanisms in adult English speaking monolinguals compared to early sequential Spanish-English bilinguals during the initial stages of novel word learning. Functional magnetic resonance imaging during a lexico-semantic task after only two hours of exposure to novel German vocabulary flashcards showed that monolinguals activated a broader set of cortical control regions associated with higher-level cognitive processes, including the supplementary motor area (SMA), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC), as well as the caudate, implicated in cognitive control of language. However, bilinguals recruited a more localized subcortical network that included the putamen, associated more with motor control of language. These results suggest that experience managing multiple languages may differentiate the learning strategy and subsequent neural mechanisms of cognitive control used by bilinguals compared to monolinguals in the early stages of novel word learning. PMID:23194816

A higher-order theory of emotional consciousness

PubMed Central

LeDoux, Joseph E.; Brown, Richard

2017-01-01

Emotional states of consciousness, or what are typically called emotional feelings, are traditionally viewed as being innately programmed in subcortical areas of the brain, and are often treated as different from cognitive states of consciousness, such as those related to the perception of external stimuli. We argue that conscious experiences, regardless of their content, arise from one system in the brain. In this view, what differs in emotional and nonemotional states are the kinds of inputs that are processed by a general cortical network of cognition, a network essential for conscious experiences. Although subcortical circuits are not directly responsible for conscious feelings, they provide nonconscious inputs that coalesce with other kinds of neural signals in the cognitive assembly of conscious emotional experiences. In building the case for this proposal, we defend a modified version of what is known as the higher-order theory of consciousness. PMID:28202735

A Rapid Subcortical Amygdala Route for Faces Irrespective of Spatial Frequency and Emotion.

PubMed

McFadyen, Jessica; Mermillod, Martial; Mattingley, Jason B; Halász, Veronika; Garrido, Marta I

2017-04-05

There is significant controversy over the existence and function of a direct subcortical visual pathway to the amygdala. It is thought that this pathway rapidly transmits low spatial frequency information to the amygdala independently of the cortex, and yet the directionality of this function has never been determined. We used magnetoencephalography to measure neural activity while human participants discriminated the gender of neutral and fearful faces filtered for low or high spatial frequencies. We applied dynamic causal modeling to demonstrate that the most likely underlying neural network consisted of a pulvinar-amygdala connection that was uninfluenced by spatial frequency or emotion, and a cortical-amygdala connection that conveyed high spatial frequencies. Crucially, data-driven neural simulations revealed a clear temporal advantage of the subcortical connection over the cortical connection in influencing amygdala activity. Thus, our findings support the existence of a rapid subcortical pathway that is nonselective in terms of the spatial frequency or emotional content of faces. We propose that that the "coarseness" of the subcortical route may be better reframed as "generalized." SIGNIFICANCE STATEMENT The human amygdala coordinates how we respond to biologically relevant stimuli, such as threat or reward. It has been postulated that the amygdala first receives visual input via a rapid subcortical route that conveys "coarse" information, namely, low spatial frequencies. For the first time, the present paper provides direction-specific evidence from computational modeling that the subcortical route plays a generalized role in visual processing by rapidly transmitting raw, unfiltered information directly to the amygdala. This calls into question a widely held assumption across human and animal research that fear responses are produced faster by low spatial frequencies. Our proposed mechanism suggests organisms quickly generate fear responses to a wide range of visual properties, heavily implicating future research on anxiety-prevention strategies. Copyright © 2017 the authors 0270-6474/17/373864-11$15.00/0.

Dopaminergic system and dream recall: An MRI study in Parkinson's disease patients.

PubMed

De Gennaro, Luigi; Lanteri, Olimpia; Piras, Fabrizio; Scarpelli, Serena; Assogna, Francesca; Ferrara, Michele; Caltagirone, Carlo; Spalletta, Gianfranco

2016-03-01

We investigated the role of the dopamine system [i.e., subcortical-medial prefrontal cortex (mPFC) network] in dreaming, by studying patients with Parkinson's Disease (PD) as a model of altered dopaminergic transmission. Subcortical volumes and cortical thickness were extracted by 3T-MR images of 27 PD patients and 27 age-matched controls, who were asked to fill out a dream diary upon morning awakening for one week. PD patients do not substantially differ from healthy controls with respect to the sleep, dream, and neuroanatomical measures. Multivariate correlational analyses in PD patients show that dopamine agonist dosage is associated to qualitatively impoverished dreams, as expressed by lower bizarreness and lower emotional load values. Visual vividness (VV) of their dream reports positively correlates with volumes of both the amygdalae and with thickness of the left mPFC. Emotional load also positively correlates with hippocampal volume. Beside the replication of our previous finding on the role of subcortical nuclei in dreaming experience of healthy subjects, this represents the first evidence of a specific role of the amygdala-mPFC dopaminergic network system in dream recall. The association in PD patients between higher dopamine agonist dosages and impoverished dream reports, however, and the significant correlations between VV and mesolimbic regions, however, provide an empirical support to the hypothesis that a dopamine network plays a key role in dream generation. The causal relation is however precluded by the intrinsic limitation of assuming the dopamine agonist dosage as a measure of the hypodopaminergic state in PD. Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Reduced structural connectivity within a prefrontal-motor-subcortical network in amyotrophic lateral sclerosis.

PubMed

Buchanan, Colin R; Pettit, Lewis D; Storkey, Amos J; Abrahams, Sharon; Bastin, Mark E

2015-05-01

To investigate white matter structural connectivity changes associated with amyotrophic lateral sclerosis (ALS) using network analysis and compare the results with those obtained using standard voxel-based methods, specifically Tract-based Spatial Statistics (TBSS). MRI data were acquired from 30 patients with ALS and 30 age-matched healthy controls. For each subject, 85 grey matter regions (network nodes) were identified from high resolution structural MRI, and network connections formed from the white matter tracts generated by diffusion MRI and probabilistic tractography. Whole-brain networks were constructed using strong constraints on anatomical plausibility and a weighting reflecting tract-averaged fractional anisotropy (FA). Analysis using Network-based Statistics (NBS), without a priori selected regions, identified an impaired motor-frontal-subcortical subnetwork (10 nodes and 12 bidirectional connections), consistent with upper motor neuron pathology, in the ALS group compared with the controls (P = 0.020). Reduced FA in three of the impaired network connections, which involved fibers of the corticospinal tract, correlated with rate of disease progression (P ≤ 0.024). A novel network-tract comparison revealed that the connections involved in the affected network had a strong correspondence (mean overlap of 86.2%) with white matter tracts identified as having reduced FA compared with the control group using TBSS. These findings suggest that white matter degeneration in ALS is strongly linked to the motor cortex, and that impaired structural networks identified using NBS have a strong correspondence to affected white matter tracts identified using more conventional voxel-based methods. © 2014 Wiley Periodicals, Inc.

Development of large-scale functional brain networks in children.

PubMed

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-07-01

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

Development of Large-Scale Functional Brain Networks in Children

PubMed Central

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-01-01

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7–9 y) and 22 young-adults (ages 19–22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

Increased subcortical neural activity among HIV+ individuals during a lexical retrieval task.

PubMed

Thames, April D; Sayegh, Philip; Terashima, Kevin; Foley, Jessica M; Cho, Andrew; Arentoft, Alyssa; Hinkin, Charles H; Bookheimer, Susan Y

2016-08-01

Deficits in lexical retrieval, present in approximately 40% of HIV+ patients, are thought to reflect disruptions to frontal-striatal functions and may worsen with immunosuppression. Coupling frontal-striatal tasks such as lexical retrieval with functional neuroimaging may help delineate the pathophysiologic mechanisms underlying HIV-associated neurological dysfunction. We examined whether HIV infection confers brain functional changes during lexical access and retrieval. It was expected that HIV+ individuals would demonstrate greater brain activity in frontal-subcortical regions despite minimal differences between groups on neuropsychological testing. Within the HIV+ sample, we examined associations between indices of immunosuppression (recent and nadir CD4+ count) and task-related signal change in frontostriatal structures. Method16 HIV+ participants and 12 HIV- controls underwent fMRI while engaged in phonemic/letter and semantic fluency tasks. Participants also completed standardized measures of verbal fluency HIV status groups performed similarly on phonemic and semantic fluency tasks prior to being scanned. fMRI results demonstrated activation differences during the phonemic fluency task as a function of HIV status, with HIV+ individuals demonstrating significantly greater activation in BG structures than HIV- individuals. There were no significant differences in frontal brain activation between HIV status groups during the phonemic fluency task, nor were there significant brain activation differences during the semantic fluency task. Within the HIV+ group, current CD4+ count, though not nadir, was positively correlated with increased activity in the inferior frontal gyrus and basal ganglia. During phonemic fluency performance, HIV+ patients recruit subcortical structures to a greater degree than HIV- controls despite similar task performances suggesting that fMRI may be sensitive to neurocompromise before overt cognitive declines can be detected. Among HIV+ individuals, reduced activity in the frontal-subcortical structures was associated with lower CD4+ count. Copyright © 2015 Elsevier Inc. All rights reserved.

Safe Resection of Gliomas of the Dominant Angular Gyrus Availing of Preoperative FMRI and Intraoperative DTI: Preliminary Series and Surgical Technique.

PubMed

D'Andrea, Giancarlo; Familiari, Pietro; Di Lauro, Antonio; Angelini, Albina; Sessa, Giovanni

2016-03-01

Language dysfunction, visual deficit, numeracy impairment, and Gerstmann syndrome often occur in the cortical area; furthermore, the subcortical white matter is the inviolable limit of "functional neurosurgery." Preoperative functional magnetic resonance imaging (fMRI) and tractography are capable of providing the data required for safe "surgical planning" at both the cortical and subcortical levels. We report our experience regarding high-grade gliomas affecting the dominant angular gyrus (AG), supramarginal gyrus (SMG), intraparietal sulcus (IPS), and their respective subcortical areas using intraoperative MRI and diffusion tensor imaging (DTI). Retrospectively, we reviewed a consecutive series of 27 patients operated in a BrainSuite for high-grade intraparenchymal tumors of the left posterior temporoparietal junction. We included tumors involving the dominant AG, SMG, and/or IPS and the subcortical course of arcuate fasciculus (AF) and all the patients who underwent preoperative fMRI and DTI to localize the AF and the eloquent cortical areas. Just after craniotomy, new volumetric MRI and DTI verified and corrected possible brain shift. After the gross total resection was carried out, and before approaching the residual mass close to the white matter tract, an intraoperative MRI was again performed. We operated on 27 patients, 15 males and 12 females, whose diagnosis was always high-grade glioma. During the preoperative neurologic examination, 6 patients were asymptomatic; 3 presented a Gerstmann syndrome; 16 showed dysphasic disturbances, 6 of which were associated with visual field deficits; and 2 showed weakness of the right limb. Our results suggest that this approach is completely safe and effective as an alternative to awake surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

[Obsessive-compulsive disorder, a new model of basal ganglia dysfunction? Elements from deep brain stimulation studies].

PubMed

Haynes, W I A; Millet, B; Mallet, L

2012-01-01

Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Role of Basal Ganglia Circuits in Resisting Interference by Distracters: A swLORETA Study

PubMed Central

Bocquillon, Perrine; Bourriez, Jean-Louis; Palmero-Soler, Ernesto; Destée, Alain; Defebvre, Luc; Derambure, Philippe; Dujardin, Kathy

2012-01-01

Background The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. Both mechanisms rely on a dorsal frontoparietal network, while focalization additionally involves a ventral frontoparietal network. The role of subcortical structures in attention is less clear, despite the fact that the striatum interacts significantly with the frontal cortex via frontostriatal loops. One means of investigating the basal ganglia's contributions to attention is to examine the features of P300 components (i.e. amplitude, latency, and generators) in patients with basal ganglia damage (such as in Parkinson's disease (PD), in which attention is often impaired). Three-stimulus oddball paradigms can be used to study distracter-elicited and target-elicited P300 subcomponents. Methodology/Principal Findings In order to compare distracter- and target-elicited P300 components, high-density (128-channel) electroencephalograms were recorded during a three-stimulus visual oddball paradigm in 15 patients with early PD and 15 matched healthy controls. For each subject, the P300 sources were localized using standardized weighted low-resolution electromagnetic tomography (swLORETA). Comparative analyses (one-sample and two-sample t-tests) were performed using SPM5® software. The swLORETA analyses showed that PD patients displayed fewer dorsolateral prefrontal (DLPF) distracter-P300 generators but no significant differences in target-elicited P300 sources; this suggests dysfunction of the DLPF cortex when the executive frontostriatal loop is disrupted by basal ganglia damage. Conclusions/Significance Our results suggest that the cortical attention frontoparietal networks (mainly the dorsal one) are modulated by the basal ganglia. Disruption of this network in PD impairs resistance to distracters, which results in attention disorders. PMID:22470542

Asymmetric pedunculopontine network connectivity in parkinsonian patients with freezing of gait

PubMed Central

Fling, Brett W.; Cohen, Rajal G.; Mancini, Martina; Nutt, John G.; Fair, Damian A.

2013-01-01

Freezing of gait is one of the most debilitating symptoms in Parkinson’s disease as it causes falls and reduces mobility and quality of life. The pedunculopontine nucleus is one of the major nuclei of the mesencephalic locomotor region and has neurons related to anticipatory postural adjustments preceding step initiation as well as to the step itself, thus it may be critical for coupling posture and gait to avoid freezing. Because freezing of gait and postural impairments have been related to frontal lesions and frontal dysfunction such as executive function, we hypothesized that freezing is associated with disrupted connectivity between midbrain locomotor regions and medial frontal cortex. We used diffusion tensor imaging to quantify structural connectivity of the pedunculopontine nucleus in patients with Parkinson’s disease with freezing of gait, without freezing, and healthy age-matched controls. We also included behavioural tasks to gauge severity of freezing of gait, quantify gait metrics, and assess executive cognitive functions to determine whether between-group differences in executive dysfunction were related to pedunculopontine nucleus structural network connectivity. Using seed regions from the pedunculopontine nucleus, we were able to delineate white matter connections between the spinal cord, cerebellum, pedunculopontine nucleus, subcortical and frontal/prefrontal cortical regions. The current study is the first to demonstrate differences in structural connectivity of the identified locomotor pathway in patients with freezing of gait. We report reduced connectivity of the pedunculopontine nucleus with the cerebellum, thalamus and multiple regions of the frontal cortex. Moreover, these structural differences were observed solely in the right hemisphere of patients with freezing of gait. Finally, we show that the more left hemisphere-lateralized the pedunculopontine nucleus tract volume, the poorer the performance on cognitive tasks requiring the initiation of appropriate actions and/or the inhibition of inappropriate actions, specifically within patients with freezing. These results support the notion that freezing of gait is strongly related to structural deficits in the right hemisphere’s locomotor network involving prefrontal cortical areas involved in executive inhibition function. PMID:23824487

Comparison of regional brain atrophy and cognitive impairment between pure akinesia with gait freezing and Richardson's syndrome

PubMed Central

Hong, Jin Yong; Yun, Hyuk Jin; Sunwoo, Mun Kyung; Ham, Jee Hyun; Lee, Jong-Min; Sohn, Young H.; Lee, Phil Hyu

2015-01-01

Pure akinesia with gait freezing (PAGF) is considered a clinical phenotype of progressive supranuclear palsy. The brain atrophy and cognitive deficits in PAGF are expected to be less prominent than in classical Richardson's syndrome (RS), but this hypothesis has not been explored yet. We reviewed the medical records of 28 patients with probable RS, 19 with PAGF, and 29 healthy controls, and compared cortical thickness, subcortical gray matter volume, and neuropsychological performance among the three groups. Patients with PAGF had thinner cortices in frontal, inferior parietal, and temporal areas compared with controls; however, areas of cortical thinning in PAGF patients were less extensive than those in RS patients. In PAGF patients, hippocampal, and thalamic volumes were also smaller than controls, whereas subcortical gray matter volumes in PAGF and RS patients were comparable. In a comparison of neuropsychological tests, PAGF patients had better cognitive performance in executive function, visual memory, and visuospatial function than RS patients had. These results demonstrate that cognitive impairment, cortical thinning, and subcortical gray matter atrophy in PAGF patients resemble to those in RS patients, though the severity of cortical thinning and cognitive dysfunction is milder. Our results suggest that, PAGF and RS may share same pathology but that it appears to affect a smaller proportion of the cortex in PAGF. PMID:26483680

Common genetic variants influence human subcortical brain structures

PubMed Central

Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

2015-01-01

The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): assessment of the involved white matter tracts by MRI.

PubMed

Kassem, Hassan; Wafaie, Ahmed; Abdelfattah, Sherif; Farid, Tarek

2014-01-01

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy (1H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable signal abnormalities in the sensory and pyramidal tracts in addition to the brainstem and cerebellar connections. Proton MRS showed consistent elevation of the lactate within the abnormal white matter. Distinct MRI findings in the form of selective affection of subcortical and deep white matter tracts of the brain (involving the posterior limb of internal capsules and sparing the subcortical U fibers), dorsal column and lateral cortico-spinal tracts of the spinal cord should lead to the diagnosis of LBSL supported by the presence of lactate peak in 1H MRS. The disease can be confirmed by the analysis of the disease gene DARS2.

Differences in cortical vs. subcortical GABAergic signaling: a candidate mechanism of electroclinical dissociation of neonatal seizures

PubMed Central

Glykys, J.; Dzhala, V.I.; Kuchibhotla, K.V.; Feng, G.; Kuner, T.; Augustine, G.; Bacskai, BJ.; Staley, KJ.

2010-01-01

Electroclinical dissociation of neonatal seizures refers to electrographic seizure activity that is not clinically manifest. Dissociation increases after treatment with Phenobarbital, which increases the GABAA receptor (GABAAR) conductance. The effects of GABAAR activation depend on the intracellular Cl− concentration ([Cl−]i) that is determined by the inward Cl− transporter NKCC1 and the outward Cl− transporter KCC2. Differential maturation of Cl− transport observed in cortical vs. subcortical regions should alter the efficacy of GABA-mediated inhibition. In perinatal rat pups, most thalamic neurons maintained low [Cl−]i, and were inhibited by GABA. Phenobarbital suppressed thalamic seizure activity. Most neocortical neurons maintained higher [Cl−]i, and were excited by GABAAR activation. Phenobarbital had insignificant anticonvulsant responses in the neocortex until NKCC1 was blocked. Regional differences in the ontogeny of Cl− transport may thus explain why seizure activity in the cortex is not suppressed by anticonvulsants that block the transmission of seizure activity through subcortical networks. PMID:19755108

Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson's disease.

PubMed

Melloni, Margherita; Sedeño, Lucas; Hesse, Eugenia; García-Cordero, Indira; Mikulan, Ezequiel; Plastino, Angelo; Marcotti, Aida; López, José David; Bustamante, Catalina; Lopera, Francisco; Pineda, David; García, Adolfo M; Manes, Facundo; Trujillo, Natalia; Ibáñez, Agustín

2015-07-08

Impairments of action language have been documented in early stage Parkinson's disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxel-based morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies.

Parcellating an Individual Subject's Cortical and Subcortical Brain Structures Using Snowball Sampling of Resting-State Correlations

PubMed Central

Wig, Gagan S.; Laumann, Timothy O.; Cohen, Alexander L.; Power, Jonathan D.; Nelson, Steven M.; Glasser, Matthew F.; Miezin, Francis M.; Snyder, Abraham Z.; Schlaggar, Bradley L.; Petersen, Steven E.

2014-01-01

We describe methods for parcellating an individual subject's cortical and subcortical brain structures using resting-state functional correlations (RSFCs). Inspired by approaches from social network analysis, we first describe the application of snowball sampling on RSFC data (RSFC-Snowballing) to identify the centers of cortical areas, subdivisions of subcortical nuclei, and the cerebellum. RSFC-Snowballing parcellation is then compared with parcellation derived from identifying locations where RSFC maps exhibit abrupt transitions (RSFC-Boundary Mapping). RSFC-Snowballing and RSFC-Boundary Mapping largely complement one another, but also provide unique parcellation information; together, the methods identify independent entities with distinct functional correlations across many cortical and subcortical locations in the brain. RSFC parcellation is relatively reliable within a subject scanned across multiple days, and while the locations of many area centers and boundaries appear to exhibit considerable overlap across subjects, there is also cross-subject variability—reinforcing the motivation to parcellate brains at the level of individuals. Finally, examination of a large meta-analysis of task-evoked functional magnetic resonance imaging data reveals that area centers defined by task-evoked activity exhibit correspondence with area centers defined by RSFC-Snowballing. This observation provides important evidence for the ability of RSFC to parcellate broad expanses of an individual's brain into functionally meaningful units. PMID:23476025

Identifying a Network of Brain Regions Involved in Aversion-Related Processing: A Cross-Species Translational Investigation

PubMed Central

Hayes, Dave J.; Northoff, Georg

2011-01-01

The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed. PMID:22102836

Automated sub-cortical brain structure segmentation combining spatial and deep convolutional features.

PubMed

Kushibar, Kaisar; Valverde, Sergi; González-Villà, Sandra; Bernal, Jose; Cabezas, Mariano; Oliver, Arnau; Lladó, Xavier

2018-06-15

Sub-cortical brain structure segmentation in Magnetic Resonance Images (MRI) has attracted the interest of the research community for a long time as morphological changes in these structures are related to different neurodegenerative disorders. However, manual segmentation of these structures can be tedious and prone to variability, highlighting the need for robust automated segmentation methods. In this paper, we present a novel convolutional neural network based approach for accurate segmentation of the sub-cortical brain structures that combines both convolutional and prior spatial features for improving the segmentation accuracy. In order to increase the accuracy of the automated segmentation, we propose to train the network using a restricted sample selection to force the network to learn the most difficult parts of the structures. We evaluate the accuracy of the proposed method on the public MICCAI 2012 challenge and IBSR 18 datasets, comparing it with different traditional and deep learning state-of-the-art methods. On the MICCAI 2012 dataset, our method shows an excellent performance comparable to the best participant strategy on the challenge, while performing significantly better than state-of-the-art techniques such as FreeSurfer and FIRST. On the IBSR 18 dataset, our method also exhibits a significant increase in the performance with respect to not only FreeSurfer and FIRST, but also comparable or better results than other recent deep learning approaches. Moreover, our experiments show that both the addition of the spatial priors and the restricted sampling strategy have a significant effect on the accuracy of the proposed method. In order to encourage the reproducibility and the use of the proposed method, a public version of our approach is available to download for the neuroimaging community. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment.

PubMed

Yi, Li-Ye; Liang, Xia; Liu, Da-Ming; Sun, Bo; Ying, Sun; Yang, Dong-Bo; Li, Qing-Bin; Jiang, Chuan-Lu; Han, Ying

2015-10-01

Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (svMCI). However, whether and how these changes alter functional brain network organization remains largely unknown. We recruited 21 patients with svMCI and 26 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging scans. Graph theory-based network analyses were used to investigate alterations in the topological organization of functional brain networks. Compared with the HC individuals, the patients with svMCI showed disrupted global network topology with significantly increased path length and modularity. Modular structure was also impaired in the svMCI patients with a notable rearrangement of the executive control module, where the parietal regions were split out and grouped as a separate module. The svMCI patients also revealed deficits in the intra- and/or intermodule connectivity of several brain regions. Specifically, the within-module degree was decreased in the middle cingulate gyrus while it was increased in the left anterior insula, medial prefrontal cortex and cuneus. Additionally, increased intermodule connectivity was observed in the inferior and superior parietal gyrus, which was associated with worse cognitive performance in the svMCI patients. Together, our results indicate that svMCI patients exhibit dysregulation of the topological organization of functional brain networks, which has important implications for understanding the pathophysiological mechanism of svMCI. © 2015 John Wiley & Sons Ltd.

Proverb Interpretation Changes in Aging

ERIC Educational Resources Information Center

Uekermann, Jennifer; Thoma, Patrizia; Daum, Irene

2008-01-01

Recent investigations have emphasized the involvement of fronto-subcortical networks to proverb comprehension. Although the prefrontal cortex is thought to be affected by normal aging, relatively little work has been carried out to investigate potential effects of aging on proverb comprehension. In the present investigation participants in three…

Resting state functional connectivity of the anterior striatum and prefrontal cortex predicts reading performance in school-age children.

PubMed

Alcauter, Sarael; García-Mondragón, Liliana; Gracia-Tabuenca, Zeus; Moreno, Martha B; Ortiz, Juan J; Barrios, Fernando A

2017-11-01

The current study investigated the neural basis of reading performance in 60 school-age Spanish-speaking children, aged 6 to 9years. By using a data-driven approach and an automated matching procedure, we identified a left-lateralized resting state network that included typical language regions (Wernicke's and Broca's regions), prefrontal cortex, pre- and post-central gyri, superior and middle temporal gyri, cerebellum, and subcortical regions, and explored its relevance for reading performance (accuracy, comprehension and speed). Functional connectivity of the left frontal and temporal cortices and subcortical regions predicted reading speed. These results extend previous findings on the relationship between functional connectivity and reading competence in children, providing new evidence about such relationships in previously unexplored regions in the resting brain, including the left caudate, putamen and thalamus. This work highlights the relevance of a broad network, functionally synchronized in the resting state, for the acquisition and perfecting of reading abilities in young children. Copyright © 2017 Elsevier Inc. All rights reserved.

Language experience differentiates prefrontal and subcortical activation of the cognitive control network in novel word learning.

PubMed

Bradley, Kailyn A L; King, Kelly E; Hernandez, Arturo E

2013-02-15

The purpose of this study was to examine the cognitive control mechanisms in adult English speaking monolinguals compared to early sequential Spanish-English bilinguals during the initial stages of novel word learning. Functional magnetic resonance imaging during a lexico-semantic task after only 2h of exposure to novel German vocabulary flashcards showed that monolinguals activated a broader set of cortical control regions associated with higher-level cognitive processes, including the supplementary motor area (SMA), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC), as well as the caudate, implicated in cognitive control of language. However, bilinguals recruited a more localized subcortical network that included the putamen, associated more with motor control of language. These results suggest that experience managing multiple languages may differentiate the learning strategy and subsequent neural mechanisms of cognitive control used by bilinguals compared to monolinguals in the early stages of novel word learning. Copyright © 2012 Elsevier Inc. All rights reserved.

Executive Dysfunctions: The Role in Attention Deficit Hyperactivity and Post-traumatic Stress Neuropsychiatric Disorders

PubMed Central

Martínez, Lía; Prada, Edward; Satler, Corina; Tavares, Maria C. H.; Tomaz, Carlos

2016-01-01

Executive functions (EFs) is an umbrella term for various cognitive processes controlled by a complex neural activity, which allow the production of different types of behaviors seeking to achieve specific objectives, one of them being inhibitory control. There is a wide consensus that clinical and behavioral alterations associated with EF, such as inhibitory control, are present in various neuropsychiatric disorders. This paper reviews the research literature on the relationship between executive dysfunction, frontal-subcortical neural circuit changes, and the psychopathological processes associated with attention deficit hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD). A revision on the role of frontal-subcortical neural circuits and their presumable abnormal functioning and the high frequency of neuropsychiatric symptoms could explain the difficulties with putting effector mechanisms into action, giving individuals the necessary tools to act efficiently in their environment. Although, neuronal substrate data about ADHD and PTSD has been reported in the literature, it is isolated. Therefore, this review highlights the overlapping of neural substrates in the symptomatology of ADHD and PTSD disorders concerning EFs, especially in the inhibitory component. Thus, the changes related to impaired EF that accompany disorders like ADHD and PTSD could be explained by disturbances that have a direct or indirect impact on the functioning of these loops. Initially, the theoretical model of EF according to current neuropsychology will be presented, focusing on the inhibitory component. In a second stage, this component will be analyzed for each of the disorders of interest, considering the clinical aspects, the etiology and the neurobiological basis. Additionally, commonalities between the two neuropsychiatric conditions will be taken into consideration from the perspectives of cognitive and emotional inhibition. Finally, the implications and future prospects for research and interventions in the area will be outlined, with the intention of contributing scientific reference information that encompasses the knowledge and understanding of executive dysfunction and its relationship with these treated disorders. PMID:27602003

The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder.

PubMed

Lu, Yi; Liang, Hongmin; Han, Dan; Mo, Yin; Li, Zongfang; Cheng, Yuqi; Xu, Xiufeng; Shen, Zonglin; Tan, Chunyan; Zhao, Wei; Zhu, Yun; Sun, Xuejin

2016-01-01

Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) network or limbic-cortico-striatal-thalamic-cortical (LCSTC) circuits in patients with major depressive disorder (MDD), but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM) changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD) and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p < 0.05). Meanwhile, the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p < 0.05). Additionally, a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity. Furthermore, probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.

3D fully convolutional networks for subcortical segmentation in MRI: A large-scale study.

PubMed

Dolz, Jose; Desrosiers, Christian; Ben Ayed, Ismail

2018-04-15

This study investigates a 3D and fully convolutional neural network (CNN) for subcortical brain structure segmentation in MRI. 3D CNN architectures have been generally avoided due to their computational and memory requirements during inference. We address the problem via small kernels, allowing deeper architectures. We further model both local and global context by embedding intermediate-layer outputs in the final prediction, which encourages consistency between features extracted at different scales and embeds fine-grained information directly in the segmentation process. Our model is efficiently trained end-to-end on a graphics processing unit (GPU), in a single stage, exploiting the dense inference capabilities of fully CNNs. We performed comprehensive experiments over two publicly available datasets. First, we demonstrate a state-of-the-art performance on the ISBR dataset. Then, we report a large-scale multi-site evaluation over 1112 unregistered subject datasets acquired from 17 different sites (ABIDE dataset), with ages ranging from 7 to 64 years, showing that our method is robust to various acquisition protocols, demographics and clinical factors. Our method yielded segmentations that are highly consistent with a standard atlas-based approach, while running in a fraction of the time needed by atlas-based methods and avoiding registration/normalization steps. This makes it convenient for massive multi-site neuroanatomical imaging studies. To the best of our knowledge, our work is the first to study subcortical structure segmentation on such large-scale and heterogeneous data. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia.

PubMed

Damaraju, E; Allen, E A; Belger, A; Ford, J M; McEwen, S; Mathalon, D H; Mueller, B A; Pearlson, G D; Potkin, S G; Preda, A; Turner, J A; Vaidya, J G; van Erp, T G; Calhoun, V D

2014-01-01

Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.

Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

PubMed Central

Damaraju, E.; Allen, E.A.; Belger, A.; Ford, J.M.; McEwen, S.; Mathalon, D.H.; Mueller, B.A.; Pearlson, G.D.; Potkin, S.G.; Preda, A.; Turner, J.A.; Vaidya, J.G.; van Erp, T.G.; Calhoun, V.D.

2014-01-01

Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical–subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences. PMID:25161896

Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder

PubMed Central

Cerliani, Leonardo; Mennes, Maarten; Thomas, Rajat M.; Di Martino, Adriana; Thioux, Marc; Keysers, Christian

2016-01-01

Importance Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. Objectives To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. Design, Setting, and Participants We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. Main Outcomes and Measures We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. Results Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t ≥ 3.13, P < .001 corrected). The strength of such connections was associated with the severity of autistic traits in the ASD group (all r ≥ 0.21, P < .0067 corrected). In addition, subcortico-cortical interaction decreased with age in the entire sample (all r ≤ −0.09, P < .012 corrected), although this association was significant only in typically developing participants (all r ≤ −0.13, P < .009 corrected). Conclusions and Relevance Our results showing ASD-related impairment in the interaction between primary sensory cortices and subcortical regions suggest that the sensory processes they subserve abnormally influence brain information processing in individuals with ASD. This might contribute to the occurrence of hyposensitivity or hypersensitivity and of difficulties in top-down regulation of behavior. PMID:26061743

Maturation of Cortico-Subcortical Structural Networks-Segregation and Overlap of Medial Temporal and Fronto-Striatal Systems in Development.

PubMed

Walhovd, Kristine B; Tamnes, Christian K; Bjørnerud, Atle; Due-Tønnessen, Paulina; Holland, Dominic; Dale, Anders M; Fjell, Anders M

2015-07-01

The brain consists of partly segregated neural circuits within which structural convergence and functional integration occurs during development. The relationship of structural cortical and subcortical maturation is largely unknown. We aimed to study volumetric development of the hippocampus and basal ganglia (caudate, putamen, pallidum, accumbens) in relation to volume changes throughout the cortex. Longitudinal MRI data were obtained across a mean interval of 2.6 years in 85 participants with an age range of 8-19 years at study start. Left and right subcortical changes were related to cortical change vertex-wise in the ipsilateral hemisphere with general linear models with age, sex, interval between scans, and mean cortical volume change as covariates. Hippocampal-cortical change relationships centered on parts of the Papez circuit, including entorhinal, parahippocampal, and isthmus cingulate areas, and lateral temporal, insular, and orbitofrontal cortices in the left hemisphere. Basal ganglia-cortical change relationships were observed in mostly nonoverlapping and more anterior cortical areas, all including the anterior cingulate. Other patterns were unique to specific basal ganglia structures, including pre-, post-, and paracentral patterns relating to putamen change. In conclusion, patterns of cortico-subcortical development as assessed by morphometric analyses in part map out segregated neural circuits at the macrostructural level. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Aggrecan-based extracellular matrix shows unique cortical features and conserved subcortical principles of mammalian brain organization in the Madagascan lesser hedgehog tenrec (Echinops telfairi Martin, 1838).

PubMed

Morawski, M; Brückner, G; Jäger, C; Seeger, G; Künzle, H; Arendt, T

2010-02-03

The Madagascan tenrecs (Afrotheria), an ancient mammalian clade, are characterized by unique brain anatomy. Striking features are an expanded paleocortex but a small and poorly differentiated neocortex devoid of a distinct granular layer IV. To investigate the organization of cortical areas we analyzed extracellular matrix components in perineuronal nets (PNs) using antibodies to aggrecan, lectin staining and hyaluronan-binding protein. Selected subcortical regions were studied to correlate the cortical patterns with features in evolutionary conserved systems. In the neocortex, paleocortex and hippocampus PNs were associated with nonpyramidal neurons. Quantitative analysis in the cerebral cortex revealed area-specific proportions and laminar distribution patterns of neurons ensheathed by PNs. Cortical PNs showed divergent structural phenotypes. Diffuse PNs forming a cotton wool-like perisomatic rim were characteristic of the paleocortex. These PNs were associated with a dense pericellular plexus of calretinin-immunoreactive fibres. Clearly contoured PNs were devoid of a calretinin-positive plexus and predominated in the neocortex and hippocampus. The organization of the extracellular matrix in subcortical nuclei followed the widely distributed mammalian type. We conclude that molecular properties of the aggrecan-based extracellular matrix are conserved during evolution of mammals; however, the matrix scaffold is adapted to specific wiring patterns of cortical and subcortical neuronal networks. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Parcellating an individual subject's cortical and subcortical brain structures using snowball sampling of resting-state correlations.

PubMed

Wig, Gagan S; Laumann, Timothy O; Cohen, Alexander L; Power, Jonathan D; Nelson, Steven M; Glasser, Matthew F; Miezin, Francis M; Snyder, Abraham Z; Schlaggar, Bradley L; Petersen, Steven E

2014-08-01

We describe methods for parcellating an individual subject's cortical and subcortical brain structures using resting-state functional correlations (RSFCs). Inspired by approaches from social network analysis, we first describe the application of snowball sampling on RSFC data (RSFC-Snowballing) to identify the centers of cortical areas, subdivisions of subcortical nuclei, and the cerebellum. RSFC-Snowballing parcellation is then compared with parcellation derived from identifying locations where RSFC maps exhibit abrupt transitions (RSFC-Boundary Mapping). RSFC-Snowballing and RSFC-Boundary Mapping largely complement one another, but also provide unique parcellation information; together, the methods identify independent entities with distinct functional correlations across many cortical and subcortical locations in the brain. RSFC parcellation is relatively reliable within a subject scanned across multiple days, and while the locations of many area centers and boundaries appear to exhibit considerable overlap across subjects, there is also cross-subject variability-reinforcing the motivation to parcellate brains at the level of individuals. Finally, examination of a large meta-analysis of task-evoked functional magnetic resonance imaging data reveals that area centers defined by task-evoked activity exhibit correspondence with area centers defined by RSFC-Snowballing. This observation provides important evidence for the ability of RSFC to parcellate broad expanses of an individual's brain into functionally meaningful units. © The Author 2013. Published by Oxford University Press.

White matter correlates of impaired attention control in major depressive disorder and healthy volunteers.

PubMed

Rizk, Mina M; Rubin-Falcone, Harry; Keilp, John; Miller, Jeffrey M; Sublette, M Elizabeth; Burke, Ainsley; Oquendo, Maria A; Kamal, Ahmed M; Abdelhameed, Mohamed A; Mann, J John

2017-11-01

Major depressive disorder (MDD) is associated with impaired attention control and alterations in frontal-subcortical connectivity. We hypothesized that attention control as assessed by Stroop task interference depends on white matter integrity in fronto-cingulate regions and assessed this relationship using diffusion tensor imaging (DTI) in MDD and healthy volunteers (HV). DTI images and Stroop task were acquired in 29 unmedicated MDD patients and 16 HVs, aged 18-65 years. The relationship between Stroop interference and fractional anisotropy (FA) was examined using region-of-interest (ROI) and tract-based spatial statistics (TBSS) analyses. ROI analysis revealed that Stroop interference correlated positively with FA in left caudal anterior cingulate cortex (cACC) in HVs (r = 0.62, p = 0.01), but not in MDD (r = -0.05, p= 0.79) even after controlling for depression severity. The left cACC was among 4 ROIs in fronto-cingulate network where FA was lower in MDD relative to HVs (F (1,41) = 8.87, p = 0.005). Additionally, TBSS showed the same group interaction of differences and correlations, although only at a statistical trend level. The modest sample size limits the generalizability of the findings. Structural connectivity of white matter network of cACC correlated with magnitude of Stroop interference in HVs, but not MDD. The cACC-frontal network, sub-serving attention control, may be disrupted in MDD. Less cognitive control may include enhanced effects of salience in HVs, or less effective response inhibition in MDD. Further studies of salience and inhibition components of executive function may better elucidate the relationship between brain white matter changes and executive dysfunction in MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered gray matter organization in children and adolescents with ADHD: a structural covariance connectome study

PubMed Central

Griffiths, K R; Grieve, S M; Kohn, M R; Clarke, S; Williams, L M; Korgaonkar, M S

2016-01-01

Although multiple studies have reported structural deficits in multiple brain regions in attention-deficit hyperactivity disorder (ADHD), we do not yet know if these deficits reflect a more systematic disruption to the anatomical organization of large-scale brain networks. Here we used a graph theoretical approach to quantify anatomical organization in children and adolescents with ADHD. We generated anatomical networks based on covariance of gray matter volumes from 92 regions across the brain in children and adolescents with ADHD (n=34) and age- and sex-matched healthy controls (n=28). Using graph theory, we computed metrics that characterize both the global organization of anatomical networks (interconnectivity (clustering), integration (path length) and balance of global integration and localized segregation (small-worldness)) and their local nodal measures (participation (degree) and interaction (betweenness) within a network). Relative to Controls, ADHD participants exhibited altered global organization reflected in more clustering or network segregation. Locally, nodal degree and betweenness were increased in the subcortical amygdalae in ADHD, but reduced in cortical nodes in the anterior cingulate, posterior cingulate, mid temporal pole and rolandic operculum. In ADHD, anatomical networks were disrupted and reflected an emphasis on subcortical local connections centered around the amygdala, at the expense of cortical organization. Brains of children and adolescents with ADHD may be anatomically configured to respond impulsively to the automatic significance of stimulus input without having the neural organization to regulate and inhibit these responses. These findings provide a novel addition to our current understanding of the ADHD connectome. PMID:27824356

Total MRI Small Vessel Disease Burden Correlates with Cognitive Performance, Cortical Atrophy, and Network Measures in a Memory Clinic Population.

PubMed

Banerjee, Gargi; Jang, Hyemin; Kim, Hee Jin; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Im, Kiho; Kwon, Hunki; Lee, Jong Min; Na, Duk L; Seo, Sang Won; Werring, David John

2018-01-01

Recent evidence suggests that combining individual imaging markers of cerebral small vessel disease (SVD) may more accurately reflect its overall burden and better correlate with clinical measures. We wished to establish the clinical relevance of the total SVD score in a memory clinic population by investigating the association with SVD score and cognitive performance, cortical atrophy, and structural network measures, after adjusting for amyloid-β burden. We included 243 patients with amnestic mild cognitive impairment (MCI), Alzheimer's disease dementia, subcortical vascular MCI, or subcortical vascular dementia. All underwent MR and [11C] PiB-PET scanning and had standardized cognitive testing. Multiple linear regression was used to evaluate the relationships between SVD score and cognition, cortical thickness, and structural network measures. Path analyses were performed to evaluate whether network disruption mediates the effects of SVD score on cortical thickness and cognition. Total SVD score was associated with the performance of frontal (β - 4.31, SE 2.09, p = 0.040) and visuospatial (β - 0.95, SE 0.44, p = 0.032) tasks, and with reduced cortical thickness in widespread brain regions. Total SVD score was negatively correlated with nodal efficiency, as well as changes in brain network organization, with evidence of reduced integration and increasing segregation. Path analyses showed that the associations between SVD score and frontal and visuospatial scores were partially mediated by decreases in their corresponding nodal efficiency and cortical thickness. Total SVD burden has clinical relevance in a memory clinic population and correlates with cognition, and cortical atrophy, as well as structural network disruption.

Does the Left Inferior Longitudinal Fasciculus Play a Role in Language? A Brain Stimulation Study

ERIC Educational Resources Information Center

Mandonnet, Emmanuel; Nouet, Aurelien; Gatignol, Peggy; Capelle, Laurent; Duffau, Hugues

2007-01-01

Although advances in diffusion tensor imaging have enabled us to better study the anatomy of the inferior longitudinal fasciculus (ILF), its function remains poorly understood. Recently, it was suggested that the subcortical network subserving the language semantics could be constituted, in parallel with the inferior occipitofrontal fasciculus, by…

Strengthening of Top-Down Frontal Cognitive Control Networks Underlying the Development of Inhibitory Control: An fMRI Effective Connectivity Study

PubMed Central

Hwang, Kai; Velanova, Katerina; Luna, Beatriz

2010-01-01

The ability to voluntarily inhibit responses to task irrelevant stimuli, which is a fundamental component of cognitive control, has a protracted development through adolescence. Prior human developmental imaging studies have found immaturities in localized brain activity in children and adolescents. However, little is known about how these regions integrate with age to form the distributed networks known to support cognitive control. In the present study, we used Granger Causality analysis to characterize developmental changes in effective connectivity underlying inhibitory control (antisaccade task) compared to reflexive responses (prosaccade task) in human participants. By childhood few top-down connectivity were evident with increased parietal interconnectivity. By adolescence connections from prefrontal cortex increased and parietal interconnectivity decreased in number. From adolescence to adulthood there was evidence of increased number and strength of frontal connections to cortical regions as well as subcortical regions. Taken together, results suggest that developmental improvements in inhibitory control may be supported by age related enhancements in top-down effective connectivity between frontal, oculomotor and subcortical regions. PMID:21084608

Random motor generation in a finger tapping task: influence of spatial contingency and of cortical and subcortical hemispheric brain lesions

PubMed Central

Annoni, J.; Pegna, A.

1997-01-01

OBJECTIVE—To test the hypothesis that, during random motor generation, the spatial contingencies inherent to the task would induce additional preferences in normal subjects, shifting their performances farther from randomness. By contrast, perceptual or executive dysfunction could alter these task related biases in patients with brain damage.
METHODS—Two groups of patients, with right and left focal brain lesions, as well as 25 right handed subjects matched for age and handedness were asked to execute a random choice motor task—namely, to generate a random series of 180 button presses from a set of 10 keys placed vertically in front of them.
RESULTS—In the control group, as in the left brain lesion group, motor generation was subject to deviations from theoretical expected randomness, similar to those when numbers are generated mentally, as immediate repetitions (successive presses on the same key) are avoided. However, the distribution of button presses was also contingent on the topographic disposition of the keys: the central keys were chosen more often than those placed at extreme positions. Small distances were favoured, particularly with the left hand. These patterns were influenced by implicit strategies and task related contingencies.
 By contrast, right brain lesion patients with frontal involvement tended to show a more square distribution of key presses—that is, the number of key presses tended to be more equally distributed. The strategies were also altered by brain lesions: the number of immediate repetitions was more frequent when the lesion involved the right frontal areas yielding a random generation nearer to expected theoretical randomness. The frequency of adjacent key presses was increased by right anterior and left posterior cortical as well as by right subcortical lesions, but decreased by left subcortical lesions.
CONCLUSIONS—Depending on the side of the lesion and the degree of cortical-subcortical involvement, the deficits take on a different aspect and direct repetions and adjacent key presses have different patterns of alterations. Motor random generation is therefore a complex task which seems to necessitate the participation of numerous cerebral structures, among which those situated in the right frontal, left posterior, and subcortical regions have a predominant role.

 PMID:9408109

Proprio-tactile integration for kinesthetic perception: an fMRI study.

PubMed

Kavounoudias, A; Roll, J P; Anton, J L; Nazarian, B; Roth, M; Roll, R

2008-01-31

This study aims to identify the cerebral networks involved in the integrative processing of somesthetic inputs for kinesthetic purposes. In particular, we investigated how muscle proprioceptive and tactile messages can result in a unified percept of one's own body movements. We stimulated either separately or conjointly these two sensory channels in order to evoke kinesthetic illusions of a clockwise rotation of 10 subjects' right hand in an fMRI environment. Results first show that, whether induced by a tactile or a proprioceptive stimulation, the kinesthetic illusion was accompanied by the activation of a very similar cerebral network including cortical and subcortical sensorimotor areas, which are also classically found in passive or imagined movement tasks. In addition, the strongest kinesthetic illusions occurred under the congruent proprio-tactile co-stimulation condition. They were specifically associated to brain area activations distinct from those evidenced under the unimodal stimulations: the inferior parietal lobule, the superior temporal sulcus, the insula-claustrum region, and the cerebellum. These findings support the hypothesis that heteromodal areas may subserve multisensory integrative mechanisms at cortical and subcortical levels. They also suggest the integrative processing might consist of detection of the spatial coherence between the two kinesthetic messages involving the inferior parietal lobule activity and of a detection of their temporal coincidence via a subcortical relay, the insula structure, usually linked to the relative synchrony of different stimuli. Finally, the involvement of the superior temporal sulcus in the feeling of biological movement and that of the cerebellum in the movement timing control are also discussed.

Experience-dependent modulation of feedback integration during singing: role of the right anterior insula.

PubMed

Kleber, Boris; Zeitouni, Anthony G; Friberg, Anders; Zatorre, Robert J

2013-04-03

Somatosensation plays an important role in the motor control of vocal functions, yet its neural correlate and relation to vocal learning is not well understood. We used fMRI in 17 trained singers and 12 nonsingers to study the effects of vocal-fold anesthesia on the vocal-motor singing network as a function of singing expertise. Tasks required participants to sing musical target intervals under normal conditions and after anesthesia. At the behavioral level, anesthesia altered pitch accuracy in both groups, but singers were less affected than nonsingers, indicating an experience-dependent effect of the intervention. At the neural level, this difference was accompanied by distinct patterns of decreased activation in singers (cortical and subcortical sensory and motor areas) and nonsingers (subcortical motor areas only) respectively, suggesting that anesthesia affected the higher-level voluntary (explicit) motor and sensorimotor integration network more in experienced singers, and the lower-level (implicit) subcortical motor loops in nonsingers. The right anterior insular cortex (AIC) was identified as the principal area dissociating the effect of expertise as a function of anesthesia by three separate sources of evidence. First, it responded differently to anesthesia in singers (decreased activation) and nonsingers (increased activation). Second, functional connectivity between AIC and bilateral A1, M1, and S1 was reduced in singers but augmented in nonsingers. Third, increased BOLD activity in right AIC in singers was correlated with larger pitch deviation under anesthesia. We conclude that the right AIC and sensory-motor areas play a role in experience-dependent modulation of feedback integration for vocal motor control during singing.

Linking sleep and general anesthesia mechanisms: this is no walkover.

PubMed

Bonhomme, V; Boveroux, P; Vanhaudenhuyse, A; Hans, P; Brichant, J F; Jaquet, O; Boly, M; Laureys, S

2011-01-01

This review aims at defining the link between physiological sleep and general anesthesia. Despite common behavioral and electrophysiological characteristics between both states, current literature suggests that the transition process between waking and sleep or anesthesia-induced alteration of consciousness is not driven by the same sequence of events. On the one hand, sleep originates in sub-cortical structures with subsequent repercussions on thalamo-cortical interactions and cortical activity. On the other hand, anesthesia seems to primarily affect the cortex with subsequent repercussions on the activity of sub-cortical networks. This discrepancy has yet to be confirmed by further functional brain imaging and electrophysiological experiments. The relationship between the observed functional modifications of brain activity during anesthesia and the known biochemical targets of hypnotic anesthetic agents also remains to be determined.

Functional brain imaging across development.

PubMed

Rubia, Katya

2013-12-01

The developmental cognitive neuroscience literature has grown exponentially over the last decade. This paper reviews the functional magnetic resonance imaging (fMRI) literature on brain function development of typically late developing functions of cognitive and motivation control, timing and attention as well as of resting state neural networks. Evidence shows that between childhood and adulthood, concomitant with cognitive maturation, there is progressively increased functional activation in task-relevant lateral and medial frontal, striatal and parieto-temporal brain regions that mediate these higher level control functions. This is accompanied by progressively stronger functional inter-regional connectivity within task-relevant fronto-striatal and fronto-parieto-temporal networks. Negative age associations are observed in earlier developing posterior and limbic regions, suggesting a shift with age from the recruitment of "bottom-up" processing regions towards "top-down" fronto-cortical and fronto-subcortical connections, leading to a more mature, supervised cognition. The resting state fMRI literature further complements this evidence by showing progressively stronger deactivation with age in anti-correlated task-negative resting state networks, which is associated with better task performance. Furthermore, connectivity analyses during the resting state show that with development increasingly stronger long-range connections are being formed, for example, between fronto-parietal and fronto-cerebellar connections, in both task-positive networks and in task-negative default mode networks, together with progressively lesser short-range connections, suggesting progressive functional integration and segregation with age. Overall, evidence suggests that throughout development between childhood and adulthood, there is progressive refinement and integration of both task-positive fronto-cortical and fronto-subcortical activation and task-negative deactivation, leading to a more mature and controlled cognition.

Trait-Related Cortical-Subcortical Dissociation in Bipolar Disorder: Analysis of Network Degree Centrality.

PubMed

Zhou, Qian; Womer, Fay Y; Kong, Lingtao; Wu, Feng; Jiang, Xiaowei; Zhou, Yifang; Wang, Dahai; Bai, Chuan; Chang, Miao; Fan, Guoguang; Xu, Ke; He, Yong; Tang, Yanqing; Wang, Fei

2017-05-01

Bipolar disorder is a systemic brain disorder. Accumulated evidence suggested that cortical-subcortical imbalance could be a trait-related pathogenic factor of bipolar disorder. Degree centrality, a robust index of focal connectivity in which the number of direct connections from one node to all nodes is counted, has not previously been studied in bipolar disorder as a whole. Resting state functional magnetic resonance imaging was performed on 52 patients with DSM-IV bipolar I disorder and 70 healthy controls recruited between September 2009 and July 2014. Degree centrality was calculated within cerebral gray matter for each subject and compared between patients with bipolar disorder and healthy controls. Hub distributions of both groups were explored. Effects of medication exposure and mood state on degree centrality, as well as cortical-subcortical degree centrality correlations, were explored. Compared to healthy controls, patients with bipolar disorder exhibited significant decrease in degree centrality in cortical regions, including the middle temporal pole, inferior temporal gyrus, and ventral prefrontal cortex, but showed significant increase in degree centrality mainly in subcortical regions, including caudate, thalamus, parahippocampal gyrus, hippocampi, anterior cingulate, insula, and amygdala, and a small portion of cortical regions, such as superior and middle frontal gyrus (P < .05, corrected). Spatial distributions of the 2 groups were very similar. No significant effects of medication exposure or mood state on degree centrality were found. Patients with bipolar disorder also showed significant decrease in cortical-subcortical degree centrality correlation (P = .003). These findings further contribute to the mounting evidence of cortical-subcortical dissociation in bipolar disorder pathophysiology. In addition, this study supports the continued development and implementation of graph-based techniques to enhance our understanding of the underlying neural mechanisms in mental disorders such as bipolar disorder, which are increasingly viewed as systemic brain disorders rather than disorders arising from disruption within a single structure or a limited number of structures. Due to the heterogeneity of our sample, as well as the small sample size of each medication and mood state subgroups, further investigation is needed to support our findings. © Copyright 2016 Physicians Postgraduate Press, Inc.

Understanding emotion with brain networks.

PubMed

Pessoa, Luiz

2018-02-01

Emotional processing appears to be interlocked with perception, cognition, motivation, and action. These interactions are supported by the brain's large-scale non-modular anatomical and functional architectures. An important component of this organization involves characterizing the brain in terms of networks. Two aspects of brain networks are discussed: brain networks should be considered as inherently overlapping (not disjoint) and dynamic (not static). Recent work on multivariate pattern analysis shows that affective dimensions can be detected in the activity of distributed neural systems that span cortical and subcortical regions. More broadly, the paper considers how we should think of causation in complex systems like the brain, so as to inform the relationship between emotion and other mental aspects, such as cognition.

The role of glia in late-life depression.

PubMed

Paradise, Matt Bennett; Naismith, Sharon Linda; Norrie, Louisa Margaret; Graeber, Manuel Benedikt; Hickie, Ian Bernard

2012-12-01

Late-life depression (LLD) has a complex and multifactoral etiology. There is growing interest in elucidating how glia, acting alone or as part of a glial-neuronal network, may contribute to the pathophysiology of depression. In this paper, we explore results from neuroimaging studies showing gray-matter volume loss in key frontal and subcortical structures implicated in LLD, and present the few histological studies that have examined neuronal and glial densities in these regions. Compared to results in younger people with depression, there appear to be age-dependent differences in neuronal pathology but the changes in glial pathology may be more subtle, perhaps reflecting a longer-term compensatory gliosis to earlier damage. We then consider the mechanisms by which both astrocytes and microglia may mediate and modulate neuronal dysfunction and possible degeneration in depression. These include a critical role in the response to peripheral inflammation and central microglial activation, as well as a key role in glutamate metabolism. Advances in our understanding of glia are highlighted, including the role of microglia as "electricians" of the brain and astrocytes as key communicating cells, an integral part of the tripartite synapse. Finally, implications for clinicians are discussed, including the consideration of glia as biomarkers for LLD and incorporation of glia into future therapeutic strategies.

A Subcortical Oscillatory Network Contributes to Recovery of Hand Dexterity after Spinal Cord Injury

ERIC Educational Resources Information Center

Nishimura, Yukio; Morichika, Yosuke; Isa, Tadashi

2009-01-01

Recent studies have shown that after partial spinal-cord lesion at the mid-cervical segment, the remaining pathways compensate for restoring finger dexterity; however, how they control hand/arm muscles has remained unclear. To elucidate the changes in dynamic properties of neural circuits connecting the motor cortex and hand/arm muscles, we…

White Matter Compromise of Callosal and Subcortical Fiber Tracts in Children with Autism Spectrum Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Lincoln, Alan J.; Muller, Ralph-Axel

2010-01-01

Objective: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle…

Development of optical neuroimaging to detect drug-induced brain functional changes in vivo

NASA Astrophysics Data System (ADS)

Du, Congwu; Pan, Yingtian

2014-03-01

Deficits in prefrontal function play a crucial role in compulsive cocaine use, which is a hallmark of addiction. Dysfunction of the prefrontal cortex might result from effects of cocaine on neurons as well as from disruption of cerebral blood vessels. However, the mechanisms underlying cocaine's neurotoxic effects are not fully understood, partially due to technical limitations of current imaging techniques (e.g., PET, fMRI) to differentiate vascular from neuronal effects at sufficiently high temporal and spatial resolutions. We have recently developed a multimodal imaging platform which can simultaneously characterize the changes in cerebrovascular hemodynamics, hemoglobin oxygenation and intracellular calcium fluorescence for monitoring the effects of cocaine on the brain. Such a multimodality imaging technique (OFI) provides several uniquely important merits, including: 1) a large field-of-view, 2) high spatiotemporal resolutions, 3) quantitative 3D imaging of the cerebral blood flow (CBF) networks, 4) label-free imaging of hemodynamic changes, 5) separation of vascular compartments (e.g., arterial and venous vessels) and monitoring of cortical brain metabolic changes, 6) discrimination of cellular (neuronal) from vascular responses. These imaging features have been further advanced in combination with microprobes to form micro-OFI that allows quantification of drug effects on subcortical brain. In addition, our ultrahigh-resolution ODT (μODT) enables 3D microangiography and quantitative imaging of capillary CBF networks. These optical strategies have been used to investigate the effects of cocaine on brain physiology to facilitate the studies of brain functional changes induced by addictive substance to provide new insights into neurobiological effects of the drug on the brain.

Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study.

PubMed

Kommajosyula, Srinivasa P; Randall, Marcus E; Brozoski, Thomas J; Odintsov, Boris M; Faingold, Carl L

2017-09-01

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to improved approaches directed at prevention of human SUDEP. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-reported personality variability across the social network is associated with interpersonal dysfunction.

PubMed

Clifton, Allan; Kuper, Laura E

2011-04-01

We describe 2 studies (n=52 and n=82) examining variability in perceptions of personality using a social network methodology. Undergraduate participants completed self-report measures of personality and interpersonal dysfunction and then subsequently reported on their personalities with each of 30 members of their social networks. Results across the 2 studies found substantial variability in participants' perceived personalities within their social networks. Measures of interpersonal dysfunction were associated with the amount of variability in dyadic ratings of personality, specifically Agreeableness and Openness to Experience. Results suggest that personality variability across interpersonal contexts may be an important individual difference related to social behavior and dysfunction. © 2011 The Authors. Journal of Personality © 2011, Wiley Periodicals, Inc.

Probing links between action perception and action production in Parkinson's disease using Fitts' law.

PubMed

Sakurada, Takeshi; Knoblich, Guenther; Sebanz, Natalie; Muramatsu, Shin-Ichi; Hirai, Masahiro

2018-03-01

Information on how the subcortical brain encodes information required to execute actions or to evaluate others' actions remains scanty. To clarify this link, Fitts'-law tasks for perception and execution were tested in patients with Parkinson's disease (PD). For the perception task, participants were shown apparent motion displays of a person moving their arm between two identical targets and reported whether they judged that the person could realistically move at the perceived speed without missing the targets. For the motor task, participants were required to touch the two targets as quickly and accurately as possible, similarly to the person observed in the perception task. In both tasks, the PD group exhibited, or imputed to others, significantly slower performances than those of the control group. However, in both groups, the relationships of perception and execution with task difficulty were exactly those predicted by Fitts' law. This suggests that despite dysfunction of the subcortical region, motor simulation abilities reflected mechanisms of compensation in the PD group. Moreover, we found that patients with PD had difficulty in switching their strategy for estimating others' actions when asked to do so. Copyright © 2018 Elsevier Ltd. All rights reserved.

Developmental kinesiology: three levels of motor control in the assessment and treatment of the motor system.

PubMed

Kobesova, Alena; Kolar, Pavel

2014-01-01

Three levels of sensorimotor control within the central nervous system (CNS) can be distinguished. During the neonatal stage, general movements and primitive reflexes are controlled at the spinal and brain stem levels. Analysis of the newborn's spontaneous general movements and the assessment of primitive reflexes is crucial in the screening and early recognition of a risk for abnormal development. Following the newborn period, the subcortical level of the CNS motor control emerges and matures mainly during the first year of life. This allows for basic trunk stabilization, a prerequisite for any phasic movement and for the locomotor function of the extremities. At the subcortical level, orofacial muscles and afferent information are automatically integrated within postural-locomotor patterns. Finally, the cortical (the highest) level of motor control increasingly becomes activated. Cortical control is important for the individual qualities and characteristics of movement. It also allows for isolated segmental movement and relaxation. A child with impaired cortical motor control may be diagnosed with developmental dyspraxia or developmental coordination disorder. Human ontogenetic models, i.e., developmental motor patterns, can be used in both the diagnosis and treatment of locomotor system dysfunction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Whole-brain MEG connectivity-based analyses reveals critical hubs in childhood absence epilepsy.

PubMed

Youssofzadeh, Vahab; Agler, William; Tenney, Jeffrey R; Kadis, Darren S

2018-06-04

Absence seizures are thought to be linked to abnormal interplays between regions of a thalamocortical network. However, the complexity of this widespread network makes characterizing the functional interactions among various brain regions challenging. Using whole-brain functional connectivity and network analysis of magnetoencephalography (MEG) data, we explored pre-treatment brain hubs ("highly connected nodes") of patients aged 6 to 12 years with childhood absence epilepsy. We analyzed ictal MEG data of 74 seizures from 16 patients. We employed a time-domain beamformer technique to estimate MEG sources in broadband (1-40 Hz) where the greatest power changes between ictal and preictal periods were identified. A phase synchrony measure, phase locking value, and a graph theory metric, eigenvector centrality (EVC), were utilized to quantify voxel-level connectivity and network hubs of ictal > preictal periods, respectively. A volumetric atlas containing 116 regions of interests (ROIs) was utilized to summarize the network measures. ROIs with EVC (z-score) > 1.96 were reported as critical hubs. ROIs analysis revealed functional-anatomical hubs in a widespread network containing bilateral precuneus (right/left, z = 2.39, 2.18), left thalamus (z = 2.28), and three anterior cerebellar subunits of lobule "IV-V" (z = 3.9), vermis "IV-V" (z = 3.57), and lobule "III" (z = 2.03). Findings suggest that highly connected brain areas or hubs are present in focal cortical, subcortical, and cerebellar regions during absence seizures. Hubs in thalami, precuneus and cingulate cortex generally support a theory of rapidly engaging and bilaterally distributed networks of cortical and subcortical regions responsible for seizures generation, whereas hubs in anterior cerebellar regions may be linked to terminating motor automatisms frequently seen during typical absence seizures. Whole-brain network connectivity is a powerful analytic tool to reveal focal components of absence seizures in MEG. Our investigations can lead to a better understanding of the pathophysiology of CAE. Copyright © 2018 Elsevier B.V. All rights reserved.

Novel bandlike signal abnormality suggestive of heterotopia in patient with a KCNQ1 frameshift mutation.

PubMed

Sabharwal, Priyanka; Devinsky, Orrin; M Shepherd, Timothy

2017-12-01

Malformations of cortical development are associated with epilepsy and cognitive dysfunction, and can occur in patients with SCN1A ion channel mutations. We report a novel and subtle bandlike subcortical heterotopia on integrated positron emission tomography-magnetic resonance imaging ( PET-MRI) in a patient with treatment-resistant epilepsy due to a de novo KCNQ1 frameshift mutation. Our case highlights the potential for other channel mutations to cause both epilepsy and cortical malformations. Further scrutiny of high contrast resolution MRI studies is warranted for patients with KCNQ1 and other epilepsy genes to further define their extended phenotype.

New Developments in Human Neurocognition: Clinical, Genetic and Brain Imaging Correlates of Impulsivity and Compulsivity

PubMed Central

Fineberg, Naomi A.; Chamberlain, Samuel R.; Goudriaan, Anna E.; Stein, Dan J.; Vanderschuren, Louk J.M.J.; Gillan, Claire M.; Shekar, Sameer; Gorwood, Philip A.P.M.; Voon, Valerie; Morein-Zamir, Sharon; Denys, Damiaan; Sahakian, Barbara J.; Moeller, F. Gerard; Robbins, Trevor W.; Potenza, Marc N.

2014-01-01

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this paper, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive and addictive disorders and indicate new directions for research. PMID:24512640

New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity.

PubMed

Fineberg, Naomi A; Chamberlain, Samuel R; Goudriaan, Anna E; Stein, Dan J; Vanderschuren, Louk J M J; Gillan, Claire M; Shekar, Sameer; Gorwood, Philip A P M; Voon, Valerie; Morein-Zamir, Sharon; Denys, Damiaan; Sahakian, Barbara J; Moeller, F Gerard; Robbins, Trevor W; Potenza, Marc N

2014-02-01

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.

Can theories of visual representation help to explain asymmetries in amygdala function?

PubMed

McMenamin, Brenton W; Marsolek, Chad J

2013-06-01

Emotional processing differs between the left and right hemispheres of the brain, and functional differences have been reported more specifically between the left and right amygdalae, subcortical structures heavily implicated in emotional processing. However, the empirical pattern of amygdalar asymmetries is inconsistent with extant theories of emotional asymmetries. Here we review this discrepancy, and we hypothesize that hemispheric differences in visual object processing help to explain the previously reported functional differences between the left and right amygdalae. The implication that perceptual factors play a large role in determining amygdalar asymmetries may help to explain amygdalar dysfunction in the development and maintenance of posttraumatic stress disorder.

Normal Pressure Hydrocephalus: Diagnosis and Treatment

PubMed Central

Shprecher, David; Schwalb, Jason; Kurlan, Roger

2009-01-01

Normal pressure hydrocephalus (NPH) is a syndrome of gait dysfunction and enlarged cerebral ventricles in the absence of another cause. It is frequently accompanied by frontal and subcortical cognitive deficits and bladder detrusor overactivity. NPH is rare relative to other potential causes of these symptoms in the elderly, but timely diagnosis can lead to reversal of symptoms through ventricular shunting. There are many tests used to predict possible response to surgery, such as MRI of the brain, formalized neuropsychological and gait testing, large-volume lumbar puncture, and prolonged lumbar drainage, but no one test has been validated to rule out potential response to surgery. PMID:18713572

[Unconscious sexual desire: fMRI and EEG evidences from self-expansion theory to mirror neurons].

PubMed

Ortigue, Stephanie; Bianchi-Demicheli, Francesco

2010-03-24

Recent advances in cognitive-social neuroscience allow a better understanding of the mechanisms underlying dyadic relationships. From a neuronal viewpoint, desire in dyadic relationships involves a specific fronto-temporo-parietal network and also a subcortical network that mediates conscious and unconscious mechanisms of reward, satisfaction, attention, self representation and self-expansion. The integration of this neuroscientific knowledge on the unconscious neurobiological activation for sexual desire in the human brain will provide physicians with new therapeutical and neuroscientific tools to apprehend sexual disorders in couple.

A method for safely resecting anterior butterfly gliomas: the surgical anatomy of the default mode network and the relevance of its preservation.

PubMed

Burks, Joshua D; Bonney, Phillip A; Conner, Andrew K; Glenn, Chad A; Briggs, Robert G; Battiste, James D; McCoy, Tressie; O'Donoghue, Daniel L; Wu, Dee H; Sughrue, Michael E

2017-06-01

OBJECTIVE Gliomas invading the anterior corpus callosum are commonly deemed unresectable due to an unacceptable risk/benefit ratio, including the risk of abulia. In this study, the authors investigated the anatomy of the cingulum and its connectivity within the default mode network (DMN). A technique is described involving awake subcortical mapping with higher attention tasks to preserve the cingulum and reduce the incidence of postoperative abulia for patients with so-called butterfly gliomas. METHODS The authors reviewed clinical data on all patients undergoing glioma surgery performed by the senior author during a 4-year period at the University of Oklahoma Health Sciences Center. Forty patients were identified who underwent surgery for butterfly gliomas. Each patient was designated as having undergone surgery either with or without the use of awake subcortical mapping and preservation of the cingulum. Data recorded on these patients included the incidence of abulia/akinetic mutism. In the context of the study findings, the authors conducted a detailed anatomical study of the cingulum and its role within the DMN using postmortem fiber tract dissections of 10 cerebral hemispheres and in vivo diffusion tractography of 10 healthy subjects. RESULTS Forty patients with butterfly gliomas were treated, 25 (62%) with standard surgical methods and 15 (38%) with awake subcortical mapping and preservation of the cingulum. One patient (1/15, 7%) experienced postoperative abulia following surgery with the cingulum-sparing technique. Greater than 90% resection was achieved in 13/15 (87%) of these patients. CONCLUSIONS This study presents evidence that anterior butterfly gliomas can be safely removed using a novel, attention-task based, awake brain surgery technique that focuses on preserving the anatomical connectivity of the cingulum and relevant aspects of the cingulate gyrus.

Basal ganglia and cerebellar interconnectivity within the human thalamus.

PubMed

Pelzer, Esther A; Melzer, Corina; Timmermann, Lars; von Cramon, D Yves; Tittgemeyer, Marc

2017-01-01

Basal ganglia and the cerebellum are part of a densely interconnected network. While both subcortical structures process information in basically segregated loops that primarily interact in the neocortex, direct subcortical interaction has been recently confirmed by neuroanatomical studies using viral transneuronal tracers in non-human primate brains. The thalamus is thought to be the main relay station of both projection systems. Yet, our understanding of subcortical basal ganglia and cerebellar interconnectivity within the human thalamus is rather sparse, primarily due to limitation in the acquisition of in vivo tracing. Consequently, we strive to characterize projections of both systems and their potential overlap within the human thalamus by diffusion MRI and tractography. Our analysis revealed a decreasing anterior-to-posterior gradient for pallido-thalamic connections in: (1) the ventral-anterior thalamus, (2) the intralaminar nuclei, and (3) midline regions. Conversely, we found a decreasing posterior-to-anterior gradient for dentato-thalamic projections predominantly in: (1) the ventral-lateral and posterior nucleus; (2) dorsal parts of the intralaminar nuclei and the subparafascicular nucleus, and (3) the medioventral and lateral mediodorsal nucleus. A considerable overlap of connectivity pattern was apparent in intralaminar nuclei and midline regions. Notably, pallidal and cerebellar projections were both hemispherically lateralized to the left thalamus. While strikingly consistent with findings from transneuronal studies in non-human primates as well as with pre-existing anatomical studies on developmentally expressed markers or pathological human brains, our assessment provides distinctive connectional fingerprints that illustrate the anatomical substrate of integrated functional networks between basal ganglia and the cerebellum. Thereby, our findings furnish useful implications for cerebellar contributions to the clinical symptomatology of movement disorders.

Comparison of Brain Activity Correlating with Self-Report versus Narrative Attachment Measures during Conscious Appraisal of an Attachment Figure.

PubMed

Yaseen, Zimri S; Zhang, Xian; Muran, J Christopher; Winston, Arnold; Galynker, Igor I

2016-01-01

The Adult Attachment Interview (AAI) has been the gold standard of attachment assessment, but requires special training. The Relationship Scales Questionnaire (RSQ) is a widely used self-report measure. We investigate how each correlates with brain activity during appraisal of subjects' mothers. Twenty-eight women were scored on the AAI, RSQ, and mood measures. During functional magnetic resonance imaging, subjects viewed their mothers in neutral-, valence-, and salience-rating conditions. We identified regions where contrasts in brain activity between appraisal and neutral viewing conditions correlated with each measure of attachment after covarying for mood. AAI and RSQ measures were then compared in terms of the extent to which regions of correlating brain activity overlapped with "default mode network" (DMN) vs. executive frontal network (EFN) masks and cortical vs. subcortical masks. Additionally, interactions with mood were examined. Salience and valence processing associated with increased thalamo-striatal, posterior cingulate, and visual cortex activity. Salience processing decreased PFC activity, whereas valence processing increased left insula activity. Activity correlating with AAI vs. RSQ measures demonstrated significantly more DMN and subcortical involvement. Interactions with mood were observed in the middle temporal gyrus and precuneus for both measures. The AAI appears to disproportionately correlate with conscious appraisal associated activity in DMN and subcortical structures, while the RSQ appears to tap EFN structures more extensively. Thus, the AAI may assess more interoceptive, 'core-self'-related processes, while the RSQ captures higher-order cognitions involved in attachment. Shared interaction effects between mood and AAI and RSQ-measures may suggest that processes tapped by each belong to a common system.

Functional Neuroimaging of Spike-Wave Seizures

PubMed Central

Motelow, Joshua E.; Blumenfeld, Hal

2013-01-01

Generalized spike-wave seizures are typically brief events associated with dynamic changes in brain physiology, metabolism, and behavior. Functional magnetic resonance imaging (fMRI) provides a relatively high spatio-temporal resolution method for imaging cortical-subcortical network activity during spike-wave seizures. Patients with spike-wave seizures often have episodes of staring and unresponsiveness which interfere with normal behavior. Results from human fMRI studies suggest that spike-wave seizures disrupt specific networks in the thalamus and fronto-parietal association cortex which are critical for normal attentive consciousness. However, the neuronal activity underlying imaging changes seen during fMRI is not well understood, particularly in abnormal conditions such as seizures. Animal models have begun to provide important fundamental insights into the neuronal basis for fMRI changes during spike-wave activity. Work from these models including both fMRI and direct neuronal recordings suggest that, like in humans, specific cortical-subcortical networks are involved in spike-wave, while other regions are spared. Regions showing fMRI increases demonstrate correlated increases in neuronal activity in animal models. The mechanisms of fMRI decreases in spike-wave will require further investigation. A better understanding of the specific brain regions involved in generating spike-wave seizures may help guide efforts to develop targeted therapies aimed at preventing or reversing abnormal excitability in these brain regions, ultimately leading to a cure for this disorder. PMID:18839093

Resting State Correlates of Subdimensions of Anxious Affect

PubMed Central

Bijsterbosch, Janine; Smith, Stephen; Forster, Sophie; John, Oliver P.; Bishop, Sonia J.

2014-01-01

Resting state fMRI may help identify markers of risk for affective disorder. Given the comorbidity of anxiety and depressive disorders and the heterogeneity of these disorders as defined by DSM, an important challenge is to identify alterations in resting state brain connectivity uniquely associated with distinct profiles of negative affect. The current study aimed to address this by identifying differences in brain connectivity specifically linked to cognitive and physiological profiles of anxiety, controlling for depressed affect. We adopted a two-stage multivariate approach. Hierarchical clustering was used to independently identify dimensions of negative affective style and resting state brain networks. Combining the clustering results, we examined individual differences in resting state connectivity uniquely associated with subdimensions of anxious affect, controlling for depressed affect. Physiological and cognitive subdimensions of anxious affect were identified. Physiological anxiety was associated with widespread alterations in insula connectivity, including decreased connectivity between insula subregions and between the insula and other medial frontal and subcortical networks. This is consistent with the insula facilitating communication between medial frontal and subcortical regions to enable control of physiological affective states. Meanwhile, increased connectivity within a frontoparietal–posterior cingulate cortex–precunous network was specifically associated with cognitive anxiety, potentially reflecting increased spontaneous negative cognition (e.g., worry). These findings suggest that physiological and cognitive anxiety comprise subdimensions of anxiety-related affect and reveal associated alterations in brain connectivity. PMID:24168223

Bridging disparate symptoms of schizophrenia: a triple network dysfunction theory

PubMed Central

Nekovarova, Tereza; Fajnerova, Iveta; Horacek, Jiri; Spaniel, Filip

2014-01-01

Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. However, the etiology of this disorder has yet to be fully understood. Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of a triple brain network model of the dysfunctional switching between default mode and central executive network (CEN) related to the aberrant activity of the salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of self (self-awareness and self-representation) and theory of mind (ToM) dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of self and ToM in schizophrenia together with neuroimaging data that support the triple brain network model as a common neuronal substrate of this dysfunction. PMID:24910597

The Role of the Auditory Brainstem in Processing Musically Relevant Pitch

PubMed Central

Bidelman, Gavin M.

2013-01-01

Neuroimaging work has shed light on the cerebral architecture involved in processing the melodic and harmonic aspects of music. Here, recent evidence is reviewed illustrating that subcortical auditory structures contribute to the early formation and processing of musically relevant pitch. Electrophysiological recordings from the human brainstem and population responses from the auditory nerve reveal that nascent features of tonal music (e.g., consonance/dissonance, pitch salience, harmonic sonority) are evident at early, subcortical levels of the auditory pathway. The salience and harmonicity of brainstem activity is strongly correlated with listeners’ perceptual preferences and perceived consonance for the tonal relationships of music. Moreover, the hierarchical ordering of pitch intervals/chords described by the Western music practice and their perceptual consonance is well-predicted by the salience with which pitch combinations are encoded in subcortical auditory structures. While the neural correlates of consonance can be tuned and exaggerated with musical training, they persist even in the absence of musicianship or long-term enculturation. As such, it is posited that the structural foundations of musical pitch might result from innate processing performed by the central auditory system. A neurobiological predisposition for consonant, pleasant sounding pitch relationships may be one reason why these pitch combinations have been favored by composers and listeners for centuries. It is suggested that important perceptual dimensions of music emerge well before the auditory signal reaches cerebral cortex and prior to attentional engagement. While cortical mechanisms are no doubt critical to the perception, production, and enjoyment of music, the contribution of subcortical structures implicates a more integrated, hierarchically organized network underlying music processing within the brain. PMID:23717294

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

PubMed

Bock, J; Breuer, S; Poeggel, G; Braun, K

2017-03-01

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers

PubMed Central

Felicio, Andre C.; Dinelle, Katherine; Agarwal, Pankaj A.; McKenzie, Jessamyn; Heffernan, Nicole; Road, Jeremy D.; Appel-Cresswell, Silke; Wszolek, Zbigniew K.; Farrer, Matthew J.; Schulzer, Michael; Sossi, Vesna; Stoessl, A. Jon

2014-01-01

Introduction We have used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome. Methods All subjects had brain imaging using 18F-6-fluoro-L-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter). Results FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate and left ventral striatum. Conclusions Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene. PMID:24797316

Primary CNS lymphoma as a cause of Korsakoff syndrome.

PubMed

Toth, Cory; Voll, Chris; Macaulay, Robert

2002-01-01

Korsakoff syndrome presents with memory dysfunction with retrograde amnesia, anterograde amnesia, limited insight into dysfunction, and confabulation. The most common etiology of Korsakoff syndrome is thiamine deficiency secondary to alcoholism. There are limited case reports of structural lesions causing Korsakoff syndrome. A 46-year-old male with a long history of alcoholism presented with a history of confusion, amnesia, and confabulation with no localizing features on neurological examination. The patient showed no clinical change with intravenous thiamine. Computed tomography of the brain revealed a heterogenous, enhancing mass lesion centered within the third ventricle, with other lesions found throughout cortical and subcortical regions. The patient was given dexamethasone i.v. without noticeable clinical improvement but with marked radiological improvement with mass reduction. Stereotactic biopsy revealed a diagnosis of primary central nervous system (CNS) lymphoma. Most patients presenting with Korsakoff syndrome have thiamine deficiency; however, mass lesions can produce an identical clinical picture. This is the first case report of a patient with primary CNS lymphoma presenting as Korsakoff syndrome.

The contribution of brain sub-cortical loops in the expression and acquisition of action understanding abilities☆

PubMed Central

Caligiore, Daniele; Pezzulo, Giovanni; Miall, R. Chris; Baldassarre, Gianluca

2013-01-01

Research on action understanding in cognitive neuroscience has led to the identification of a wide “action understanding network” mainly encompassing parietal and premotor cortical areas. Within this cortical network mirror neurons are critically involved implementing a neural mechanism according to which, during action understanding, observed actions are reflected in the motor patterns for the same actions of the observer. We suggest that focusing only on cortical areas and processes could be too restrictive to explain important facets of action understanding regarding, for example, the influence of the observer's motor experience, the multiple levels at which an observed action can be understood, and the acquisition of action understanding ability. In this respect, we propose that aside from the cortical action understanding network, sub-cortical processes pivoting on cerebellar and basal ganglia cortical loops could crucially support both the expression and the acquisition of action understanding abilities. Within the paper we will discuss how this extended view can overcome some limitations of the “pure” cortical perspective, supporting new theoretical predictions on the brain mechanisms underlying action understanding that could be tested by future empirical investigations. PMID:23911926

The brain of opera singers: experience-dependent changes in functional activation.

PubMed

Kleber, B; Veit, R; Birbaumer, N; Gruzelier, J; Lotze, M

2010-05-01

Several studies have shown that motor-skill training over extended time periods results in reorganization of neural networks and changes in brain morphology. Yet, little is known about training-induced adaptive changes in the vocal system, which is largely subserved by intrinsic reflex mechanisms. We investigated highly accomplished opera singers, conservatory level vocal students, and laymen during overt singing of an Italian aria in a neuroimaging experiment. We provide the first evidence that the training of vocal skills is accompanied by increased functional activation of bilateral primary somatosensory cortex representing articulators and larynx. Opera singers showed additional activation in right primary sensorimotor cortex. Further training-related activation comprised the inferior parietal lobe and bilateral dorsolateral prefrontal cortex. At the subcortical level, expert singers showed increased activation in the basal ganglia, the thalamus, and the cerebellum. A regression analysis of functional activation with accumulated singing practice confirmed that vocal skills training correlates with increased activity of a cortical network for enhanced kinesthetic motor control and sensorimotor guidance together with increased involvement of implicit motor memory areas at the subcortical and cerebellar level. Our findings may have ramifications for both voice rehabilitation and deliberate practice of other implicit motor skills that require interoception.

Neuroimaging of love: fMRI meta-analysis evidence toward new perspectives in sexual medicine.

PubMed

Ortigue, Stephanie; Bianchi-Demicheli, Francesco; Patel, Nisa; Frum, Chris; Lewis, James W

2010-11-01

Brain imaging is becoming a powerful tool in the study of human cerebral functions related to close personal relationships. Outside of subcortical structures traditionally thought to be involved in reward-related systems, a wide range of neuroimaging studies in relationship science indicate a prominent role for different cortical networks and cognitive factors. Thus, the field needs a better anatomical/network/whole-brain model to help translate scientific knowledge from lab bench to clinical models and ultimately to the patients suffering from disorders associated with love and couple relationships. The aim of the present review is to provide a review across wide range of functional magnetic resonance imaging (fMRI) studies to critically identify the cortical networks associated with passionate love, and to compare and contrast it with other types of love (such as maternal love and unconditional love for persons with intellectual disabilities). Retrospective review of pertinent neuroimaging literature. Review of published literature on fMRI studies of love illustrating brain regions associated with different forms of love. Although all fMRI studies of love point to the subcortical dopaminergic reward-related brain systems (involving dopamine and oxytocin receptors) for motivating individuals in pair-bonding, the present meta-analysis newly demonstrated that different types of love involve distinct cerebral networks, including those for higher cognitive functions such as social cognition and bodily self-representation. These metaresults provide the first stages of a global neuroanatomical model of cortical networks involved in emotions related to different aspects of love. Developing this model in future studies should be helpful for advancing clinical approaches helpful in sexual medicine and couple therapy. © 2010 International Society for Sexual Medicine.

Nicotinic α4β2 acetylcholine receptors and cognitive function in Parkinson's disease.

PubMed

Lorenz, R; Samnick, S; Dillmann, U; Schiller, M; Ong, M F; Faßbender, K; Buck, A; Spiegel, J

2014-09-01

Idiopathic Parkinson's disease (IPD) is characterized by the clinical motor symptoms of hypokinesia, rigidity, and tremor. Apart from these motor symptoms, cognitive deficits often occur in IPD. The positive effect of cholinesterase inhibitors on cognitive deficits in IPD and findings of earlier molecular imaging studies suggest that the cholinergic system plays an important role in the origin of cognitive decline in IPD. Twenty-five non-demented patients with IPD underwent a 5-[123I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380) SPECT to visualize α4β2 nicotinic acetylcholine receptors (nAchR) and cognitive testing with the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) battery to identify domains of cognitive dysfunction. In the CERAD, the IPD patients exhibited deficits in non-verbal memory, attention, psychomotor velocity, visuoconstructive ability, and executive functions. After Bonferroni correction for multiple comparisons, we found significant correlations between performance of the CERAD subtests Boston Naming Test (a specific test for visual perception and for detection of word-finding difficulties) and Word List Intrusions (a specific test for learning capacity and memory for language information) vs binding of α4β2 nAchR in cortical (the right superior parietal lobule) and subcortical areas (the left thalamus, the left posterior subcortical region, and the right posterior subcortical region). These significant correlations between the results of the CERAD subtests and the cerebral α4β2 nAchR density, as assessed by 5-I-A-85380 SPECT, indicate that cerebral cholinergic pathways are relevant to cognitive processing in IPD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study

PubMed Central

Aghakhanyan, Gayane; Bonanni, Paolo; Randazzo, Giovanna; Nappi, Sara; Tessarotto, Federica; De Martin, Lara; Frijia, Francesca; De Marchi, Daniele; De Masi, Francesco; Kuppers, Beate; Lombardo, Francesco; Caramella, Davide; Montanaro, Domenico

2016-01-01

Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS. PMID:27626634

Gene expression links functional networks across cortex and striatum.

PubMed

Anderson, Kevin M; Krienen, Fenna M; Choi, Eun Young; Reinen, Jenna M; Yeo, B T Thomas; Holmes, Avram J

2018-04-12

The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks. Network-associated expression is consistent across independent human datasets and evolutionarily conserved in non-human primates. Genes preferentially expressed within the limbic network (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and temporal pole) relate to risk for psychiatric illness, chloride channel complexes, and markers of somatostatin neurons. Somato/motor associated genes are enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses indicate that parallel cortico-striatal processing channels possess dissociable genetic signatures that recapitulate distributed functional networks, and nominate molecular mechanisms supporting cortico-striatal circuitry in health and disease.

Magnetoencephalographic imaging of deep corticostriatal network activity during a rewards paradigm.

PubMed

Kanal, Eliezer Y; Sun, Mingui; Ozkurt, Tolga E; Jia, Wenyan; Sclabassi, Robert

2009-01-01

The human rewards network is a complex system spanning both cortical and subcortical regions. While much is known about the functions of the various components of the network, research on the behavior of the network as a whole has been stymied due to an inability to detect signals at a high enough temporal resolution from both superficial and deep network components simultaneously. In this paper, we describe the application of magnetoencephalographic imaging (MEG) combined with advanced signal processing techniques to this problem. Using data collected while subjects performed a rewards-related gambling paradigm demonstrated to activate the rewards network, we were able to identify neural signals which correspond to deep network activity. We also show that this signal was not observable prior to filtration. These results suggest that MEG imaging may be a viable tool for the detection of deep neural activity.

Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei.

PubMed

Feng, Li; Motelow, Joshua E; Ma, Chanthia; Biche, William; McCafferty, Cian; Smith, Nicholas; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro; Blumenfeld, Hal

2017-11-22

The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal maintenance, but its precise seizure-associated functions are not known. We recorded neuronal activity in three different thalamic regions and found divergent activity patterns, which may respectively participate in seizure propagation, impaired level of conscious arousal, and altered relay of information to the cortex during focal limbic seizures. These very different activity patterns within the thalamus may help explain why focal temporal lobe seizures often disrupt widespread network function, and can help guide future treatments aimed at restoring normal thalamocortical network activity and cognition. Copyright © 2017 the authors 0270-6474/17/3711441-14$15.00/0.

Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei

PubMed Central

Feng, Li; Motelow, Joshua E.; Ma, Chanthia; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro

2017-01-01

The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal maintenance, but its precise seizure-associated functions are not known. We recorded neuronal activity in three different thalamic regions and found divergent activity patterns, which may respectively participate in seizure propagation, impaired level of conscious arousal, and altered relay of information to the cortex during focal limbic seizures. These very different activity patterns within the thalamus may help explain why focal temporal lobe seizures often disrupt widespread network function, and can help guide future treatments aimed at restoring normal thalamocortical network activity and cognition. PMID:29066556

Changes in cortico-subcortical and subcortico-subcortical connectivity impact cognitive control to emotional cues across development

PubMed Central

Cohen, Alexandra O.; Dreyfuss, Michael F. W.; Casey, B. J.

2016-01-01

The capacity to suppress inappropriate thoughts, emotions and actions in favor of appropriate ones shows marked changes throughout childhood and adolescence. Most research has focused on pre-frontal circuit development to explain these changes. Yet, subcortical circuitry involving the amygdala and ventral striatum (VS) has been shown to modulate cue-triggered motivated behaviors in rodents. The nature of the interaction between these two subcortical regions in humans is less well understood, especially during development when there appears to be heightened sensitivity to emotional cues. In the current study, we tested how task-based cortico-subcortical and subcortico-subcortical functional connectivity in 155 participants ages from 5 to 32 impacted cognitive control performance on an emotional go/nogo task. Functional connectivity between the amygdala and VS was inversely correlated with age and predicted cognitive control to emotional cues, when controlling for performance to neutral cues. In contrast, increased medial pre-frontal-amygdala connectivity was associated with better cognitive control to emotional cues and this cortical-subcortical connectivity mediated the association between amygdala-VS connectivity and emotional cognitive control. These findings suggest a dissociation in how subcortical-subcortical and cortical-subcortical connectivity impact cognitive control across development. PMID:27445212

White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis.

PubMed

Dimond, Dennis; Ishaque, Abdullah; Chenji, Sneha; Mah, Dennell; Chen, Zhang; Seres, Peter; Beaulieu, Christian; Kalra, Sanjay

2017-03-01

Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract-based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain-specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co-localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249-1268, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Limited plastic potential of the left ventral premotor cortex in speech articulation: evidence from intraoperative awake mapping in glioma patients.

PubMed

van Geemen, Kim; Herbet, Guillaume; Moritz-Gasser, Sylvie; Duffau, Hugues

2014-04-01

Despite previous lesional and functional neuroimaging studies, the actual role of the left ventral premotor cortex (vPMC), i.e., the lateral part of the precentral gyrus, is still poorly known. We report a series of eight patients with a glioma involving the left vPMC, who underwent awake surgery with intraoperative cortical and subcortical language mapping. The function of the vPMC, its subcortical connections, and its reorganization potential are investigated in the light of surgical findings and language outcome after resection. Electrostimulation of both the vPMC and subcortical white matter tract underneath the vPMC, that is, the anterior segment of the lateral part of the superior longitudinal fascicle (SLF), induced speech production disturbances with anarthria in all cases. Moreover, although some degrees of redistribution of the vPMC have been found in four patients, allowing its partial resection with no permanent speech disorders, this area was nonetheless still detected more medially in the precentral gyrus in the eight patients, despite its invasion by the glioma. Moreover, a direct connection of the vPMC with the SLF was preserved in all cases. Our original data suggest that the vPMC plays a crucial role in the speech production network and that its plastic potential is limited. We propose that this limitation is due to an anatomical constraint, namely the necessity for the left vPMC to remain connected to the lateral SLF. Beyond fundamental implications, such knowledge may have clinical applications, especially in surgery for tumors involving this cortico-subcortical circuit. Copyright © 2013 Wiley Periodicals, Inc.

Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity.

PubMed

Ekman, Matthias; Fiebach, Christian J; Melzer, Corina; Tittgemeyer, Marc; Derrfuss, Jan

2016-03-09

The ability to temporarily store and manipulate information in working memory is a hallmark of human intelligence and differs considerably across individuals, but the structural brain correlates underlying these differences in working memory capacity (WMC) are only poorly understood. In two separate studies, diffusion MRI data and WMC scores were collected for 70 and 109 healthy individuals. Using a combination of probabilistic tractography and network analysis of the white matter tracts, we examined whether structural brain network properties were predictive of individual WMC. Converging evidence from both studies showed that lateral prefrontal cortex and posterior parietal cortex of high-capacity individuals are more densely connected compared with low-capacity individuals. Importantly, our network approach was further able to dissociate putative functional roles associated with two different pathways connecting frontal and parietal regions: a corticocortical pathway and a subcortical pathway. In Study 1, where participants were required to maintain and update working memory items, the connectivity of the direct and indirect pathway was predictive of WMC. In contrast, in Study 2, where participants were required to maintain working memory items without updating, only the connectivity of the direct pathway was predictive of individual WMC. Our results suggest an important dissociation in the circuitry connecting frontal and parietal regions, where direct frontoparietal connections might support storage and maintenance, whereas subcortically mediated connections support the flexible updating of working memory content. Copyright © 2016 the authors 0270-6474/16/362894-10$15.00/0.

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

PubMed Central

Dubey, Mohit; Brouwers, Eelke; Hamilton, Eline M.C.; Stiedl, Oliver; Bugiani, Marianna; Koch, Henner; Kole, Maarten H.P.; Boschert, Ursula; Wykes, Robert C.; Mansvelder, Huibert D.; van der Knaap, Marjo S.

2018-01-01

Objective Loss of function of the astrocyte‐specific protein MLC1 leads to the childhood‐onset leukodystrophy “megalencephalic leukoencephalopathy with subcortical cysts” (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. Methods We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole‐cell patch‐clamp recordings and K+‐sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. Results An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice. Interpretation Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636–649 PMID:29466841

Cerebrovascular diseases and depression: epidemiology, mechanisms and treatment.

PubMed

Göthe, F; Enache, D; Wahlund, L O; Winblad, B; Crisby, M; Lökk, J; Aarsland, D

2012-09-01

Both cerebrovascular disease (CVD) and depression are common conditions in the elderly, and there is emerging evidence of a bi-directional relationship: 1) depression can cause CVD and stroke, transient ischemic attack; and 2) subcortical CVD are associated with increased risk for depression. The frequency of poststroke depression is highest during the first month after the stroke, but remains high even after several years. Depression is associated with poorer functional prognosis and higher mortality after stroke. There is good evidence that severity of functional impairment, high neuroticism, low social support as well as genetic factors are associated with an increased risk for post-stroke depression. Deep white matter lesions are the most consistent imaging correlate of depression. Potential mechanisms mediating the association between depression and CVD are neuroinflammation and HPA-axis activation, fronto-subcortical circuit lesions, and serotonergic dysfunction. Antidepressants have demonstrated effect on poststroke depression in meta-analyses, and such drugs as well as vitamin B can reduce the incidence of depression in stroke survivors. In addition, serotonergic drugs may strengthen poststroke motor and cognitive recovery, potentially through restorative mechanisms. Psychotherapeutic strategies such as problem-solving therapy seem to be effective. There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis.

Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia.

PubMed

Ko, Ji Hyun; Katako, Audrey; Aljuaid, Maram; Goertzen, Andrew L; Borys, Andrew; Hobson, Douglas E; Kim, Seok Min; Lee, Chong Sik

2017-12-01

We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [ 18 F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Mapping grey matter reductions in schizophrenia: an anatomical likelihood estimation analysis of voxel-based morphometry studies.

PubMed

Fornito, A; Yücel, M; Patti, J; Wood, S J; Pantelis, C

2009-03-01

Voxel-based morphometry (VBM) is a popular tool for mapping neuroanatomical changes in schizophrenia patients. Several recent meta-analyses have identified the brain regions in which patients most consistently show grey matter reductions, although they have not examined whether such changes reflect differences in grey matter concentration (GMC) or grey matter volume (GMV). These measures assess different aspects of grey matter integrity, and may therefore reflect different pathological processes. In this study, we used the Anatomical Likelihood Estimation procedure to analyse significant differences reported in 37 VBM studies of schizophrenia patients, incorporating data from 1646 patients and 1690 controls, and compared the findings of studies using either GMC or GMV to index grey matter differences. Analysis of all studies combined indicated that grey matter reductions in a network of frontal, temporal, thalamic and striatal regions are among the most frequently reported in literature. GMC reductions were generally larger and more consistent than GMV reductions, and were more frequent in the insula, medial prefrontal, medial temporal and striatal regions. GMV reductions were more frequent in dorso-medial frontal cortex, and lateral and orbital frontal areas. These findings support the primacy of frontal, limbic, and subcortical dysfunction in the pathophysiology of schizophrenia, and suggest that the grey matter changes observed with MRI may not necessarily result from a unitary pathological process.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

PubMed

Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

2017-03-01

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions.

PubMed

Durazzo, Timothy C; Meyerhoff, Dieter J; Yoder, Karmen K; Murray, Donna E

2017-08-01

Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers. Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined. Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM. Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions. Published by Elsevier B.V.

Specific contributions of basal ganglia and cerebellum to the neural tracking of rhythm.

PubMed

Nozaradan, Sylvie; Schwartze, Michael; Obermeier, Christian; Kotz, Sonja A

2017-10-01

How specific brain networks track rhythmic sensory input over time remains a challenge in neuroimaging work. Here we show that subcortical areas, namely the basal ganglia and the cerebellum, specifically contribute to the neural tracking of rhythm. We tested patients with focal lesions in either of these areas and healthy controls by means of electroencephalography (EEG) while they listened to rhythmic sequences known to induce selective neural tracking at a frequency corresponding to the most-often perceived pulse-like beat. Both patients and controls displayed neural responses to the rhythmic sequences. However, these response patterns were different across groups, with patients showing reduced tracking at beat frequency, especially for the more challenging rhythms. In the cerebellar patients, this effect was specific to the rhythm played at a fast tempo, which places high demands on the temporally precise encoding of events. In contrast, basal ganglia patients showed more heterogeneous responses at beat frequency specifically for the most complex rhythm, which requires more internal generation of the beat. These findings provide electrophysiological evidence that these subcortical structures selectively shape the neural representation of rhythm. Moreover, they suggest that the processing of rhythmic auditory input relies on an extended cortico-subcortico-cortical functional network providing specific timing and entrainment sensitivities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Morphological, electrophysiological, and synaptic properties of corticocallosal pyramidal cells in the neonatal rat neocortex.

PubMed

Le Bé, Jean-Vincent; Silberberg, Gilad; Wang, Yun; Markram, Henry

2007-09-01

Neocortical pyramidal cells (PCs) project to various cortical and subcortical targets. In layer V, the population of thick tufted PCs (TTCs) projects to subcortical targets such as the tectum, brainstem, and spinal cord. Another population of layer V PCs projects via the corpus callosum to the contralateral neocortical hemisphere mediating information transfer between the hemispheres. This subpopulation (corticocallosally projecting cells [CCPs]) has been previously described in terms of their morphological properties, but less is known about their electrophysiological properties, and their synaptic connectivity is unknown. We studied the morphological, electrophysiological, and synaptic properties of CCPs by retrograde labeling with fluorescent microbeads in P13-P16 Wistar rats. CCPs were characterized by shorter, untufted apical dendrites, which reached only up to layers II/III, confirming previous reports. Synaptic connections between CCPs were different from those observed between TTCs, both in probability of occurrence and dynamic properties. We found that the CCP network is about 4 times less interconnected than the TTC network and the probability of release is 24% smaller, resulting in a more linear synaptic transmission. The study shows that layer V pyramidal neurons projecting to different targets form subnetworks with specialized connectivity profiles, in addition to the specialized morphological and electrophysiological intrinsic properties.

Distinct pathways of neural coupling for different basic emotions.

PubMed

Tettamanti, Marco; Rognoni, Elena; Cafiero, Riccardo; Costa, Tommaso; Galati, Dario; Perani, Daniela

2012-01-16

Emotions are complex events recruiting distributed cortical and subcortical cerebral structures, where the functional integration dynamics within the involved neural circuits in relation to the nature of the different emotions are still unknown. Using fMRI, we measured the neural responses elicited by films representing basic emotions (fear, disgust, sadness, happiness). The amygdala and the associative cortex were conjointly activated by all basic emotions. Furthermore, distinct arrays of cortical and subcortical brain regions were additionally activated by each emotion, with the exception of sadness. Such findings informed the definition of three effective connectivity models, testing for the functional integration of visual cortex and amygdala, as regions processing all emotions, with domain-specific regions, namely: i) for fear, the frontoparietal system involved in preparing adaptive motor responses; ii) for disgust, the somatosensory system, reflecting protective responses against contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal cortices involved in understanding joyful interactions. Consistently with these domain-specific models, the results of the effective connectivity analysis indicate that the amygdala is involved in distinct functional integration effects with cortical networks processing sensorimotor, somatosensory, or cognitive aspects of basic emotions. The resulting effective connectivity networks may serve to regulate motor and cognitive behavior based on the quality of the induced emotional experience. Copyright © 2011. Published by Elsevier Inc.

Distinctive Resting State Network Disruptions Among Alzheimer's Disease, Subcortical Vascular Dementia, and Mixed Dementia Patients.

PubMed

Kim, Hee Jin; Cha, Jungho; Lee, Jong-Min; Shin, Ji Soo; Jung, Na-Yeon; Kim, Yeo Jin; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

2016-01-01

Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls. When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.

A neural circuit covarying with social hierarchy in macaques.

PubMed

Noonan, MaryAnn P; Sallet, Jerome; Mars, Rogier B; Neubert, Franz X; O'Reilly, Jill X; Andersson, Jesper L; Mitchell, Anna S; Bell, Andrew H; Miller, Karla L; Rushworth, Matthew F S

2014-09-01

Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

A Neural Circuit Covarying with Social Hierarchy in Macaques

PubMed Central

Neubert, Franz X.; O'Reilly, Jill X.; Andersson, Jesper L.; Mitchell, Anna S.; Bell, Andrew H.; Miller, Karla L.; Rushworth, Matthew F. S.

2014-01-01

Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status. PMID:25180883

Differences in Paracingulate Connectivity Associated with Epileptiform Discharges and Uncontrolled Seizures in Genetic Generalized Epilepsy

PubMed Central

Kay, Benjamin P; Holland, Scott K; Privitera, Michael D; Szaflarski, Jerzy P

2014-01-01

Summary Objective Patients with genetic generalized epilepsy (GGE) frequently continue to suffer from seizures despite appropriate clinical management. GGE is associated with changes in the resting-state networks modulated by clinical factors such as duration of disease and response to treatment. However, the effect of GSWDs and/or seizures on resting-state functional connectivity (RSFC) is not well understood. Methods We investigated the effects of GSWD frequency (in GGE patients), GGE (patients vs. healthy controls), and seizures (uncontrolled vs. controlled) on RSFC using seed-based voxel correlation in simultaneous EEG and resting-state fMRI (EEG/fMRI) data from 72 GGE patients (23 w/uncontrolled seizures) and 38 healthy controls. We used seeds in paracingulate cortex, thalamus, cerebellum, and posterior cingulate cortex to examine changes in cortical-subcortical resting-state networks and the default mode network (DMN). We excluded from analyses time points surrounding GSWDs to avoid possible contamination of the resting state. Results (1) Higher frequency of GSWDs was associated with an increase in seed-based voxel correlation with cortical and subcortical brain regions associated with executive function, attention, and the DMN, (2) RSFC in patients with GGE, when compared to healthy controls, was increased between paracingulate cortex and anterior, but not posterior, thalamus, and (3) GGE patients with uncontrolled seizures exhibited decreased cereballar RSFC. Significance Our findings in this large sample of patients with GGE (1) demonstrate an effect of interictal GSWDs on resting-state networks, (2) provide evidence that different thalamic nuclei may be affected differently by GGE, and (3) suggest that cerebellum is a modulator of ictogenic circuits. PMID:24447031

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

PubMed

Raine, A; Meloy, J R; Bihrle, S; Stoddard, J; LaCasse, L; Buchsbaum, M S

1998-01-01

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

Basal ganglia and beyond: The interplay between motor and cognitive aspects in Parkinson's disease rehabilitation.

PubMed

Ferrazzoli, Davide; Ortelli, Paola; Madeo, Graziella; Giladi, Nir; Petzinger, Giselle M; Frazzitta, Giuseppe

2018-07-01

Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions, affecting the motor behaviour. We summarize evidence that the interplay between motor and cognitive approaches is crucial in PD rehabilitation. Rehabilitation is complementary to pharmacological therapy and effective in reducing the PD disturbances, probably acting by inducing neuroplastic effects. The motor behaviour results from a complex integration between cortical and subcortical areas, underlying the motor, cognitive and motivational aspects of movement. The close interplay amongst these areas makes possible to learn, control and express habitual-automatic actions, which are dysfunctional in PD. The physiopathology of PD could be considered the base for the development of effective rehabilitation treatments. As the volitional action control is spared in early-medium stages of disease, rehabilitative approaches engaging cognition permit to achieve motor benefits and appear to be the most effective for PD. We will point out data supporting the relevance of targeting both motor and cognitive aspects in PD rehabilitation. Finally, we will discuss the role of cognitive engagement in motor rehabilitation for PD. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dual Neural Network Model for the Evolution of Speech and Language.

PubMed

Hage, Steffen R; Nieder, Andreas

2016-12-01

Explaining the evolution of speech and language poses one of the biggest challenges in biology. We propose a dual network model that posits a volitional articulatory motor network (VAMN) originating in the prefrontal cortex (PFC; including Broca's area) that cognitively controls vocal output of a phylogenetically conserved primary vocal motor network (PVMN) situated in subcortical structures. By comparing the connections between these two systems in human and nonhuman primate brains, we identify crucial biological preadaptations in monkeys for the emergence of a language system in humans. This model of language evolution explains the exclusiveness of non-verbal communication sounds (e.g., cries) in infants with an immature PFC, as well as the observed emergence of non-linguistic vocalizations in adults after frontal lobe pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Difficulty with learning of exercise instructions associated with 'working memory' dysfunction and frontal glucose hypometabolism in a patient with very mild subcortical vascular dementia with knee osteoarthritis.

PubMed

Takeda, Kenji; Meguro, Kenichi; Tanaka, Naofumi; Nakatsuka, Masahiro

2013-07-25

We present a patient with no dementia, depression or apathy, who had difficulty in learning self-exercise instructions. The patient was an 80-year-old right-handed woman who was admitted to a rehabilitation unit to receive postoperative rehabilitation after a femoral neck fracture. She was instructed quadriceps isometric exercises to perform 10 repetitions and to hold each stretch for 10 s. She performed the exercise correctly with motivation, but she had difficulty in learning the number of repetitions and the duration of each stretch. She had no history of cerebrovascular accident and the neurological examination was normal. Neuropsychological testing, MRI and (18)F-fluoro- D-glucose-positron emission tomography (FDG-PET) were performed to examine the neural mechanisms associated with this difficulty in learning instructions. Neuropsychological tests revealed dysfunction of working memory while other cognitive domains were relatively preserved. Her neuropsychological tests scores were (1) Mini-Mental State Examination: 24 (mild cognitive impairment), (2) Geriatric Depression Scale-15: 2 (no depression), (3) Apathy Scale: 2 (no apathy), (4) digit span forward: 5 (normal), (5) digit span backward: 2 (impaired), (6) visuospatial span forward: 4 (normal), (7) visuospatial span backward: 2 (impaired), (8) frontal assessment battery: 11 (normal), (9) Weigl test: 0 (impaired), (10) trail making test A: 52 s (normal), (11) train making test B: failed (impaired). T2-weighted and fluid-attenuated inversion recovery MRI showed high signal-intensity lesions in the cerebral deep white matter. FDG-PET revealed hypometabolic areas in the bilateral frontal lobes, particularly in the bilateral dorsolateral frontal area, anterior cingulate cortex and orbitofrontal cortex. One of the possible neural mechanisms underlying the learning difficulties in this patient may have been partial blockage of the cingulofrontal network by deep white matter lesions.

The role of social relationships in the link between olfactory dysfunction and mortality.

PubMed

Leschak, Carrianne J; Eisenberger, Naomi I

2018-01-01

Recent work suggests that olfactory dysfunction is a strong predictor of five-year mortality in older adults. Based on past work showing: 1) that olfactory dysfunction impairs social functioning and 2) that social ties are linked with mortality, the current work explored whether impairments in social life mediated the relationship between olfactory dysfunction and mortality. Additionally, based on work showing gender differences in the social consequences of olfactory dysfunction, gender was assessed as a potential moderator of this association. Social network size mediated the olfactory-mortality link for females. To probe what feature of social networks was driving this effect, we investigated two subcomponents of social life: emotional closeness (e.g., perceived social support, loneliness) and physical closeness (e.g., physical contact, in-person socializing with others). Physical closeness significantly mediated the olfactory-mortality link for females, even after controlling for social network size. Emotional closeness did not mediate this link. Possible mechanisms underlying this relationship are discussed.

Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications.

PubMed

Goldstein, Rita Z; Volkow, Nora D

2011-10-20

The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.

Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications

PubMed Central

Goldstein, Rita Z.; Volkow, Nora D.

2012-01-01

The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will. PMID:22011681

Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

PubMed

Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M

2016-08-01

SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep behaviour disorder and Parkinson's disease relative to each other and to controls. Connectivity measures of basal ganglia network dysfunction differentiated both rapid eye movement sleep behaviour disorder and Parkinson's disease from controls with high sensitivity (96%) and specificity (74% for rapid eye movement sleep behaviour disorder, 78% for Parkinson's disease), indicating its potential as an indicator of early basal ganglia dysfunction. Rapid eye movement sleep behaviour disorder was indistinguishable from Parkinson's disease on resting state functional magnetic resonance imaging despite obvious differences on dopamine transported single photon emission computerized tomography. Basal ganglia connectivity is a promising biomarker for the detection of early basal ganglia network dysfunction, and may help to identify patients at risk of developing Parkinson's disease in the future. Future risk stratification using a polymodal approach could combine basal ganglia network connectivity with clinical and other imaging measures, with important implications for future neuroprotective trials in rapid eye movement sleep behaviour disorder. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease

PubMed Central

Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A.; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C.; Mackay, Clare E.

2016-01-01

Abstract See Postuma (doi:10.1093/aww131) for a scientific commentary on this article. Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson’s disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson’s disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson’s disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson’s disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson’s disease and 10 control subjects received 123I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep behaviour disorder and Parkinson’s disease relative to each other and to controls. Connectivity measures of basal ganglia network dysfunction differentiated both rapid eye movement sleep behaviour disorder and Parkinson’s disease from controls with high sensitivity (96%) and specificity (74% for rapid eye movement sleep behaviour disorder, 78% for Parkinson’s disease), indicating its potential as an indicator of early basal ganglia dysfunction. Rapid eye movement sleep behaviour disorder was indistinguishable from Parkinson’s disease on resting state functional magnetic resonance imaging despite obvious differences on dopamine transported single photon emission computerized tomography. Basal ganglia connectivity is a promising biomarker for the detection of early basal ganglia network dysfunction, and may help to identify patients at risk of developing Parkinson’s disease in the future. Future risk stratification using a polymodal approach could combine basal ganglia network connectivity with clinical and other imaging measures, with important implications for future neuroprotective trials in rapid eye movement sleep behaviour disorder. PMID:27297241

From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer’s Disease

PubMed Central

Dulla, Chris G.; Coulter, Douglas A.; Ziburkus, Jokubas

2015-01-01

Complex circuitry with feed-forward and feed-back systems regulate neuronal activity throughout the brain. Cell biological, electrical, and neurotransmitter systems enable neural networks to process and drive the entire spectrum of cognitive, behavioral, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits relies on hundreds, if not thousands, of unique molecular interactions. Even single molecule dysfunctions can be disrupting to neural circuit activity, leading to neurological pathology. Here, we sample our current understanding of how molecular aberrations lead to disruptions in networks using three neurological pathologies as exemplars: epilepsy, traumatic brain injury (TBI), and Alzheimer’s disease (AD). Epilepsy provides a window into how total destabilization of network balance can occur. TBI is an abrupt physical disruption that manifests in both acute and chronic neurological deficits. Last, in AD progressive cell loss leads to devastating cognitive consequences. Interestingly, all three of these neurological diseases are interrelated. The goal of this review, therefore, is to identify molecular changes that may lead to network dysfunction, elaborate on how altered network activity and circuit structure can contribute to neurological disease, and suggest common threads that may lie at the heart of molecular circuit dysfunction. PMID:25948650

From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer's Disease.

PubMed

Dulla, Chris G; Coulter, Douglas A; Ziburkus, Jokubas

2016-06-01

Complex circuitry with feed-forward and feed-back systems regulate neuronal activity throughout the brain. Cell biological, electrical, and neurotransmitter systems enable neural networks to process and drive the entire spectrum of cognitive, behavioral, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits relies on hundreds, if not thousands, of unique molecular interactions. Even single molecule dysfunctions can be disrupting to neural circuit activity, leading to neurological pathology. Here, we sample our current understanding of how molecular aberrations lead to disruptions in networks using three neurological pathologies as exemplars: epilepsy, traumatic brain injury (TBI), and Alzheimer's disease (AD). Epilepsy provides a window into how total destabilization of network balance can occur. TBI is an abrupt physical disruption that manifests in both acute and chronic neurological deficits. Last, in AD progressive cell loss leads to devastating cognitive consequences. Interestingly, all three of these neurological diseases are interrelated. The goal of this review, therefore, is to identify molecular changes that may lead to network dysfunction, elaborate on how altered network activity and circuit structure can contribute to neurological disease, and suggest common threads that may lie at the heart of molecular circuit dysfunction. © The Author(s) 2015.

Risk factors for selective cognitive decline in dialyzed patients with end-stage renal disease: evidence from verbal fluency analysis.

PubMed

Harciarek, Michał; Williamson, John B; Biedunkiewicz, Bogdan; Lichodziejewska-Niemierko, Monika; Dębska-Ślizień, Alicja; Rutkowski, Bolesław

2012-01-01

Although dialyzed patients often have cognitive problems, little is known about the nature of these deficits. We hypothesized that, in contrast to semantic fluency relying mainly on temporal lobes, phonemic fluency, preferentially depending on functions of frontal-subcortical systems, would be particularly sensitive to the constellation of physiological pathological processes associated with end-stage renal disease and dialysis. Therefore, we longitudinally compared phonemic and semantic fluency performance between 49 dialyzed patients and 30 controls. Overall, patients performed below controls only on the phonemic fluency task. Furthermore, their performance on this task declined over time, whereas there was no change in semantic fluency. Moreover, this decline was related to the presence of hypertension and higher blood urea nitrogen. We suggest that these findings may be due to a combination of vascular and topic effects that impact more on fronto-subcortical than temporal lobe networks, but this speculation requires direct confirmation.

Advanced Fault Diagnosis Methods in Molecular Networks

PubMed Central

Habibi, Iman; Emamian, Effat S.; Abdi, Ali

2014-01-01

Analysis of the failure of cell signaling networks is an important topic in systems biology and has applications in target discovery and drug development. In this paper, some advanced methods for fault diagnosis in signaling networks are developed and then applied to a caspase network and an SHP2 network. The goal is to understand how, and to what extent, the dysfunction of molecules in a network contributes to the failure of the entire network. Network dysfunction (failure) is defined as failure to produce the expected outputs in response to the input signals. Vulnerability level of a molecule is defined as the probability of the network failure, when the molecule is dysfunctional. In this study, a method to calculate the vulnerability level of single molecules for different combinations of input signals is developed. Furthermore, a more complex yet biologically meaningful method for calculating the multi-fault vulnerability levels is suggested, in which two or more molecules are simultaneously dysfunctional. Finally, a method is developed for fault diagnosis of networks based on a ternary logic model, which considers three activity levels for a molecule instead of the previously published binary logic model, and provides equations for the vulnerabilities of molecules in a ternary framework. Multi-fault analysis shows that the pairs of molecules with high vulnerability typically include a highly vulnerable molecule identified by the single fault analysis. The ternary fault analysis for the caspase network shows that predictions obtained using the more complex ternary model are about the same as the predictions of the simpler binary approach. This study suggests that by increasing the number of activity levels the complexity of the model grows; however, the predictive power of the ternary model does not appear to be increased proportionally. PMID:25290670

Memory Dysfunction

PubMed Central

Matthews, Brandy R.

2015-01-01

Purpose of Review: This article highlights the dissociable human memory systems of episodic, semantic, and procedural memory in the context of neurologic illnesses known to adversely affect specific neuroanatomic structures relevant to each memory system. Recent Findings: Advances in functional neuroimaging and refinement of neuropsychological and bedside assessment tools continue to support a model of multiple memory systems that are distinct yet complementary and to support the potential for one system to be engaged as a compensatory strategy when a counterpart system fails. Summary: Episodic memory, the ability to recall personal episodes, is the subtype of memory most often perceived as dysfunctional by patients and informants. Medial temporal lobe structures, especially the hippocampal formation and associated cortical and subcortical structures, are most often associated with episodic memory loss. Episodic memory dysfunction may present acutely, as in concussion; transiently, as in transient global amnesia (TGA); subacutely, as in thiamine deficiency; or chronically, as in Alzheimer disease. Semantic memory refers to acquired knowledge about the world. Anterior and inferior temporal lobe structures are most often associated with semantic memory loss. The semantic variant of primary progressive aphasia (svPPA) is the paradigmatic disorder resulting in predominant semantic memory dysfunction. Working memory, associated with frontal lobe function, is the active maintenance of information in the mind that can be potentially manipulated to complete goal-directed tasks. Procedural memory, the ability to learn skills that become automatic, involves the basal ganglia, cerebellum, and supplementary motor cortex. Parkinson disease and related disorders result in procedural memory deficits. Most memory concerns warrant bedside cognitive or neuropsychological evaluation and neuroimaging to assess for specific neuropathologies and guide treatment. PMID:26039844

Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity.

PubMed

Holsen, L M; Savage, C R; Martin, L E; Bruce, A S; Lepping, R J; Ko, E; Brooks, W M; Butler, M G; Zarcone, J R; Goldstein, J M

2012-05-01

The majority of research on obesity (OB) has focused primarily on clinical features (eating behavior, adiposity measures) or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions that are associated with appetite-regulatory hormones are also involved in the development and maintenance of OB. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic OB. Simple (non-PWS) OB represents an OB-control state. This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (that is, hypothalamus, amygdala) and prefrontal regions associated with cognitive control (that is, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) after eating. A total of 14 individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC and DLPFC. Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in the hypothalamus and hippocampus in response to food (vs non-food) images pre-meal. Post meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared with OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. In PWS, compared with OB per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple OB.

Importance of Reward and Prefrontal Circuitry in Hunger and Satiety: Prader-Willi Syndrome vs. Simple Obesity

PubMed Central

Holsen, Laura M.; Savage, Cary R.; Martin, Laura E.; Bruce, Amanda S.; Lepping, Rebecca J.; Ko, Eunice; Brooks, William M.; Butler, Merlin G.; Zarcone, Jennifer R.; Goldstein, Jill M.

2011-01-01

Background The majority of research on obesity has focused primarily on clinical features (eating behavior, adiposity measures), or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions which are associated with appetite-regulatory hormones are also involved in the development and maintenance of obesity. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic obesity. Simple (non-PWS) obesity (OB) represents an obesity control state. Objective This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (i.e., hypothalamus, amygdala) and prefrontal regions associated with cognitive control [i.e., dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC)] after eating. Design and Participants Fourteen individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls (HWC) viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC, and DLPFC. Results Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in hypothalamus and hippocampus, in response to food (vs. non-food) images pre-meal. Post-meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared to OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. Conclusion In PWS compared with obesity per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple obesity. PMID:22024642

Genetic and environmental influences on mean diffusivity and volume in subcortical brain regions.

PubMed

Gillespie, Nathan A; Neale, Michael C; Hagler, Donald J; Eyler, Lisa T; Fennema-Notestine, Christine; Franz, Carol E; Lyons, Michael J; McEvoy, Linda K; Dale, Anders M; Panizzon, Matthew S; Kremen, William S

2017-05-01

Increased mean diffusivity (MD) is hypothesized to reflect tissue degeneration and may provide subtle indicators of neuropathology as well as age-related brain changes in the absence of volumetric differences. Our aim was to determine the degree to which genetic and environmental variation in subcortical MD is distinct from variation in subcortical volume. Data were derived from a sample of 387 male twins (83 MZ twin pairs, 55 DZ twin pairs, and 111 incomplete twin pairs) who were MRI scanned as part of the Vietnam Era Twin Study of Aging. Quantitative estimates of MD and volume for 7 subcortical regions were obtained: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens. After adjusting for covariates, bivariate twin models were fitted to estimate the size and significance of phenotypic, genotypic, and environmental correlations between MD and volume at each subcortical region. With the exception of the amygdala, familial aggregation in MD was entirely explained by additive genetic factors across all subcortical regions with estimates ranging from 46 to 84%. Based on bivariate twin modeling, variation in subcortical MD appears to be both genetically and environmentally unrelated to individual differences in subcortical volume. Therefore, subcortical MD may be an alternative biomarker of brain morphology for complex traits worthy of future investigation. Hum Brain Mapp 38:2589-2598, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sparsity enables estimation of both subcortical and cortical activity from MEG and EEG

PubMed Central

Krishnaswamy, Pavitra; Obregon-Henao, Gabriel; Ahveninen, Jyrki; Khan, Sheraz; Iglesias, Juan Eugenio; Hämäläinen, Matti S.; Purdon, Patrick L.

2017-01-01

Subcortical structures play a critical role in brain function. However, options for assessing electrophysiological activity in these structures are limited. Electromagnetic fields generated by neuronal activity in subcortical structures can be recorded noninvasively, using magnetoencephalography (MEG) and electroencephalography (EEG). However, these subcortical signals are much weaker than those generated by cortical activity. In addition, we show here that it is difficult to resolve subcortical sources because distributed cortical activity can explain the MEG and EEG patterns generated by deep sources. We then demonstrate that if the cortical activity is spatially sparse, both cortical and subcortical sources can be resolved with M/EEG. Building on this insight, we develop a hierarchical sparse inverse solution for M/EEG. We assess the performance of this algorithm on realistic simulations and auditory evoked response data, and show that thalamic and brainstem sources can be correctly estimated in the presence of cortical activity. Our work provides alternative perspectives and tools for characterizing electrophysiological activity in subcortical structures in the human brain. PMID:29138310

Functional network dysfunction in anxiety and anxiety disorders

PubMed Central

Sylvester, C.M.; Corbetta, M.; Raichle, M.E.; Rodebaugh, T.; Schlaggar, B.L.; Sheline, Y.I.; Zorumski, C.F.; Lenze, E.J.

2012-01-01

A recent paradigm shift in systems neuroscience is the division of the human brain into functional networks. Functional networks are collections of brain regions with strongly correlated activity both at rest and during cognitive tasks, and each network is believed to implement a different aspect of cognition. Here, we propose that anxiety disorders and high trait anxiety are associated with a particular pattern of functional network dysfunction: increased functioning of the cingulo-opercular and ventral attention networks as well as decreased functioning of the fronto-parietal and default mode networks. This functional network model can be used to differentiate the pathology of anxiety disorders from other psychiatric illnesses such as major depression and provides targets for novel treatment strategies. PMID:22658924

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

PubMed

Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

2018-05-01

Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

On the Viability of Diffusion MRI-Based Microstructural Biomarkers in Ischemic Stroke

PubMed Central

Boscolo Galazzo, Ilaria; Brusini, Lorenza; Obertino, Silvia; Zucchelli, Mauro; Granziera, Cristina; Menegaz, Gloria

2018-01-01

Recent tract-based analyses provided evidence for the exploitability of 3D-SHORE microstructural descriptors derived from diffusion MRI (dMRI) in revealing white matter (WM) plasticity. In this work, we focused on the main open issues left: (1) the comparative analysis with respect to classical tensor-derived indices, i.e., Fractional Anisotropy (FA) and Mean Diffusivity (MD); and (2) the ability to detect plasticity processes in gray matter (GM). Although signal modeling in GM is still largely unexplored, we investigated their sensibility to stroke-induced microstructural modifications occurring in the contralateral hemisphere. A more complete picture could provide hints for investigating the interplay of GM and WM modulations. Ten stroke patients and ten age/gender-matched healthy controls were enrolled in the study and underwent diffusion spectrum imaging (DSI). Acquisitions at three and two time points (tp) were performed on patients and controls, respectively. For all subjects and acquisitions, FA and MD were computed along with 3D-SHORE-based indices [Generalized Fractional Anisotropy (GFA), Propagator Anisotropy (PA), Return To the Axis Probability (RTAP), Return To the Plane Probability (RTPP), and Mean Square Displacement (MSD)]. Tract-based analysis involving the cortical, subcortical and transcallosal motor networks and region-based analysis in GM were successively performed, focusing on the contralateral hemisphere to the stroke. Reproducibility of all the indices on both WM and GM was quantitatively proved on controls. For tract-based, longitudinal group analyses revealed the highest significant differences across the subcortical and transcallosal networks for all the indices. The optimal regression model for predicting the clinical motor outcome at tp3 included GFA, PA, RTPP, and MSD in the subcortical network in combination with the main clinical information at baseline. Region-based analysis in the contralateral GM highlighted the ability of anisotropy indices in discriminating between groups mainly at tp1, while diffusivity indices appeared to be altered at tp2. 3D-SHORE indices proved to be suitable in probing plasticity in both WM and GM, further confirming their viability as a novel family of biomarkers in ischemic stroke in WM and revealing their potential exploitability in GM. Their combination with tensor-derived indices can provide more detailed insights of the different tissue modulations related to stroke pathology. PMID:29515362

Regional cerebral changes and functional connectivity during the observation of negative emotional stimuli in subjects with post-traumatic stress disorder.

PubMed

Mazza, Monica; Tempesta, Daniela; Pino, Maria Chiara; Catalucci, Alessia; Gallucci, Massimo; Ferrara, Michele

2013-10-01

Patients with post-traumatic stress disorder (PTSD) exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional dysfunction. The aim of this study was to investigate the functional connectivity between the areas activated during emotional processing of negative stimuli in a sample of individuals affected by PTSD compared to a group of healthy subjects. Ten subjects with PTSD (who survived the L'Aquila 2009 earthquake) and ten healthy controls underwent fMRI during which the participants observed 80 images: 40 pictures with negative emotional valence and 40 neutral (scrambled) stimuli. A higher activation was found in the left posterior (LP) insula for PTSD group and in the ventromedial prefrontal cortex (vmPFC) for the healthy group. Two sets of Granger causality modeling analyses were performed to examine the directed influence from LP-insula and vmPFC to other brain regions. Activity in the vmPFC in the healthy group while observing negative stimuli predicted activity in several subcortical regions and insula, while in the PTSD group the LP-insula exerted a positive directed influence on several cortical regions. The hyperactivation in PTSD subjects of subcortical areas such as the insula would underlie the emotional, social, and relational difficulties of PTSD patients.

Extra-hippocampal subcortical limbic involvement predicts episodic recall performance in multiple sclerosis.

PubMed

Dineen, Robert A; Bradshaw, Christopher M; Constantinescu, Cris S; Auer, Dorothee P

2012-01-01

Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging. 34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, P<.0005) and mammillary body volumes (age-adjusted means 0.114 ml vs. 0.126 ml, P<.023). Multivariate regression analysis identified fornix FA and mammillary bodies as predictor of visual recall (R(2) = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R(2) = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency. These findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.

Frontal Assessment Battery as a Useful Tool to Differentiate Mild Cognitive Impairment due to Subcortical Ischemic Vascular Disease from Alzheimer Disease.

PubMed

Hsu, Yen-Hsuan; Huang, Ching-Feng; Lo, Chung-Ping; Wang, Tzu-Lan; Yang, Chi-Cheng; Tu, Min-Chien

2016-01-01

Prominent executive dysfunction can differentiate vascular dementia from Alzheimer disease (AD). However, it is unclear whether the Frontal Assessment Battery (FAB) screening tool can differentiate subcortical ischemic vascular disease (SIVD) from AD at the pre-dementia stage. In addition, the neural correlates of FAB performance have yet to be clarified. Patients with mild cognitive impairment (MCI) due to SIVD (MCI-V), MCI due to AD (MCI-A), and demographically matched controls completed the Mini-Mental State Examination, Taiwanese FAB (TFAB), Category Fluency, and Chinese Version of the Verbal Learning Test, and underwent magnetic resonance imaging. White matter hyperintensities were rated according to the Scheltens scale. TFAB total scale and its Orthographical Fluency subtest were the only measures that could differentiate MCI-V from MCI-A. Discriminative analysis showed that Orthographical Fluency scores successfully identified 73.2% of the cases with MCI-V, with 85.0% sensitivity. Orthographical Fluency scores were specifically associated with lesion load within frontal periventricular, frontal deep white matter, and basal ganglia regions. The TFAB, and especially its 1-min Orthographical Fluency subtest, is a useful screening procedure to differentiate MCI due to SIVD from MCI due to AD. The discriminative ability is probably due to frontosubcortical white matter pathologies disproportionately involved in the two disease entities. © 2016 S. Karger AG, Basel.

Fair play: social norm compliance failures in behavioural variant frontotemporal dementia.

PubMed

O'Callaghan, Claire; Bertoux, Maxime; Irish, Muireann; Shine, James M; Wong, Stephanie; Spiliopoulos, Leonidas; Hodges, John R; Hornberger, Michael

2016-01-01

Adherence to social norms is compromised in a variety of neuropsychiatric conditions. Functional neuroimaging studies have investigated social norm compliance in healthy individuals, leading to the identification of a network of fronto-subcortical regions that underpins this ability. However, there is a lack of corroborative evidence from human lesion models investigating the structural anatomy of norm compliance across this fronto-subcortical network. To address this, we developed a neuroeconomic task to investigate social norm compliance in a neurodegenerative lesion model: behavioural variant frontotemporal dementia, a condition characterized by gross social dysfunction. The task assessed norm compliance across three behaviours that are well-studied in the neuroeconomics literature: fairness, prosocial and punishing behaviours. We administered our novel version of the Ultimatum Game in 22 patients with behavioural variant frontotemporal dementia and 22 age-matched controls, to assess how decision-making behaviour was modulated in response to (i) fairness of monetary offers; and (ii) social context of monetary offers designed to produce either prosocial or punishing behaviours. Voxel-based morphometry was used to characterize patterns of grey matter atrophy associated with task performance. Acceptance rates between patients and controls were equivalent when only fairness was manipulated. However, patients were impaired in modulating their decisions in response to social contextual information. Patients' performance in the punishment condition was consistent with a reduced tendency to engage in punishment; this was associated with decreased grey matter volume in the anterior cingulate, orbitofrontal cortex, left dorsolateral prefrontal cortex and right inferior frontal gyrus. In the prosocial condition, patients' performance suggested a reduced expression of prosocial behaviour, associated with decreased grey matter in the anterior insula, lateral orbitofrontal cortex, anterior cingulate and dorsal striatum. Acceptance rates in the Ultimatum Game were also significantly related to impairments in the everyday expression of empathic concern. In conclusion, we demonstrate that compliance to basic social norms (fairness) can be maintained in behavioural variant frontotemporal dementia; however, more complex normative behaviours (prosociality, punishment) that require integration of social contextual information are disrupted in association with atrophy in key fronto-striatal regions. These results suggest that the integration of social contextual information to guide normative behaviour is uniquely impaired in behavioural variant frontotemporal dementia, and may explain other common features of the condition including gullibility and impaired empathy. Our findings also converge with previous functional neuroimaging investigations in healthy individuals and provide the first description of the structural anatomy of social norm compliance in a neurodegenerative lesion model. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Morphological MRI characteristics of recent small subcortical infarcts.

PubMed

Gattringer, Thomas; Eppinger, Sebastian; Pinter, Daniela; Pirpamer, Lukas; Berghold, Andrea; Wünsch, Gerit; Ropele, Stefan; Wardlaw, Joanna M; Enzinger, Christian; Fazekas, Franz

2015-10-01

New imaging criteria for recent small subcortical infarcts have recently been proposed, replacing the earlier term 'lacunar infarction', but their applicability and impact on lesion selection is yet unknown. To collect information on the morphologic characteristics and variability of recent small subcortical infarcts on magnetic resonance imaging in regard to lesion location and demographic variables. We identified all patients with acute stroke and cerebral magnetic resonance imaging from 2008 to 2013 in our hospital database and selected those with a single recent small subcortical infarct defined by an estimated maximal axial diameter of 20 mm. Recent small subcortical infarcts were segmented on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence to calculate the largest axial and longitudinal diameter and lesion volume. We assessed morphometric differences of recent small subcortical infarcts regarding location and demographic variables and the impact of different recent small subcortical infarct definitions on lesion selection. Three hundred forty-four patients (median age 72; range 25-92 years, 65% male) were selected. Most recent small subcortical infarcts were located in the basal ganglia (n = 111), followed by pons (n = 92), thalamus (n = 77), and centrum semiovale (n = 64). Quantitative measurements confirmed visual assessment of the axial diameter in 95%. All morphometric variables were strongly intercorrelated and comparable on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence. Recent small subcortical infarcts in the basal ganglia were significantly larger both in the axial and longitudinal direction compared with other regions. Dichotomization of recent small subcortical infarcts according to axial (≤ / >15 mm) or longitudinal (≤ / >20 mm) sizes resulted in different regional frequencies and distributions. Age, gender, and time from stroke onset to magnetic resonance imaging did not influence lesion metrics or the distribution of recent small subcortical infarcts. Our study confirms the recent neuroimaging criteria for recent small subcortical infarcts as a practical concept. Definitions of the maximal axial and longitudinal diameter have a significant impact on the frequency and distribution of selected infarcts, which has to be considered for future studies. © 2015 World Stroke Organization.

Probing the frontostriatal loops involved in executive and limbic processing via interleaved TMS and functional MRI at two prefrontal locations: a pilot study.

PubMed

Hanlon, Colleen A; Canterberry, Melanie; Taylor, Joseph J; DeVries, William; Li, Xingbao; Brown, Truman R; George, Mark S

2013-01-01

The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by Alexander et al. (1986) the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial cortical-subcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment. Seventeen healthy individuals received interleaved TMS-BOLD imaging with the coil positioned over the dorsolateral (EEG: F3) and ventromedial PFC (EEG: FP1). BOLD signal change was calculated in the areas directly stimulated by the coil and in subcortical regions with afferent and efferent connectivity to the TMS target areas. Additionally, five individuals were tested on two occasions to determine test-retest reliability. Region of interest analysis revealed that TMS at both prefrontal sites led to significant BOLD signal increases in the cortex under the coil, in the striatum, and the thalamus, but not in the visual cortex (negative control region). There was a significantly larger BOLD signal change in the caudate following medial PFC TMS, relative to lateral TMS. The hippocampus in contrast was significantly more activated by lateral TMS. Post-hoc voxel-based analysis revealed that within the caudate the location of peak activity was in the ventral caudate following medial TMS and the dorsal caudate following lateral TMS. Test-retest reliability data revealed consistent BOLD responses to TMS within each individual but a large variation between individuals. These data demonstrate that, through an optimized TMS/BOLD sequence over two unique prefrontal targets, it is possible to selectively interrogate the patency of these established cortical-subcortical networks in healthy individuals, and potentially patient populations.

Brain Structure and Organization Five Decades After Childhood Onset Epilepsy

PubMed Central

Garcia-Ramos, Camille; Bobholz, Sam; Dabbs, Kevin; Hermann, Bruce; Joutsa, Juho; Rinne, Juha O.; Karrasch, Mira; Prabhakaran, Vivek; Shinnar, Shlomo; Sillanpää, Matti

2017-01-01

The purpose of this project was to characterize brain structure and organization in persons with active and remitted childhood onset epilepsy 50 years after diagnosis compared to healthy controls. Participants from a population-based investigation of uncomplicated childhood onset epilepsy were followed up 5 decades later. Forty-one participants had a history of childhood onset epilepsy (mean age of onset= 5.2 yrs, current chronological age= 56.0 yrs) and were compared to 48 population-based controls (mean age= 55.9 yrs). Of the epilepsy participants, 8 had persisting active epilepsy and in 33 the epilepsy had remitted. All participants underwent 3T MRI with subsequent vertex analysis of cortical volume, thickness, surface area and gyral complexity. In addition, cortical and subcortical volumes, including regions of the frontal, parietal, temporal, and occipital lobes, and subcortical structures including amygdala, thalamus, and hippocampus, were analyzed using graph theory techniques. There were modest group differences in traditional vertex-based analyses of cortical volume, thickness, surface area and gyral index, as well as across volumes of subcortical structures, after correction for multiple comparisons. Graph theory analyses revealed suboptimal topological structural organization with enhanced network segregation and reduced global integration in the epilepsy participants compared to controls, these patterns significantly more extreme in the active epilepsy group. Furthermore, both groups with epilepsy presented a greater number of higher Z-score regions in betweenness centrality (BC) than lower Z-score regions compared to controls. Also, contrary to the group with remitted epilepsy, patients with active epilepsy presented most of their high BC Z-score regions in subcortical areas including the amygdala, thalamus, hippocampus, pallidum and accumbens. Overall, this population-based investigation of long term outcome (5 decades) of childhood onset epilepsy reveals persisting abnormalities, especially when examined by graph theoretical measurements, and provides new insights into the very long term outcomes of active and remitted epilepsy. PMID:28370719

Automated image segmentation using support vector machines

NASA Astrophysics Data System (ADS)

Powell, Stephanie; Magnotta, Vincent A.; Andreasen, Nancy C.

2007-03-01

Neurodegenerative and neurodevelopmental diseases demonstrate problems associated with brain maturation and aging. Automated methods to delineate brain structures of interest are required to analyze large amounts of imaging data like that being collected in several on going multi-center studies. We have previously reported on using artificial neural networks (ANN) to define subcortical brain structures including the thalamus (0.88), caudate (0.85) and the putamen (0.81). In this work, apriori probability information was generated using Thirion's demons registration algorithm. The input vector consisted of apriori probability, spherical coordinates, and an iris of surrounding signal intensity values. We have applied the support vector machine (SVM) machine learning algorithm to automatically segment subcortical and cerebellar regions using the same input vector information. SVM architecture was derived from the ANN framework. Training was completed using a radial-basis function kernel with gamma equal to 5.5. Training was performed using 15,000 vectors collected from 15 training images in approximately 10 minutes. The resulting support vectors were applied to delineate 10 images not part of the training set. Relative overlap calculated for the subcortical structures was 0.87 for the thalamus, 0.84 for the caudate, 0.84 for the putamen, and 0.72 for the hippocampus. Relative overlap for the cerebellar lobes ranged from 0.76 to 0.86. The reliability of the SVM based algorithm was similar to the inter-rater reliability between manual raters and can be achieved without rater intervention.

What is the impact of child abuse on gray matter abnormalities in individuals with major depressive disorder: a case control study.

PubMed

Ahn, Sung Jun; Kyeong, Sunghyon; Suh, Sang Hyun; Kim, Jae-Jin; Chung, Tae-Sub; Seok, Jeong-Ho

2016-11-14

Patients with major depressive disorder (MDD) present heterogeneous clinical symptoms, and childhood abuse is associated with deepening of psychopathology. The aim of this study was to identify structural brain abnormalities in MDD and to assess further differences in gray matter density (GMD) associated with childhood abuse in MDD. Differences in regional GMD between 34 MDD patients and 26 healthy controls were assessed using magnetic resonance imaging and optimized voxel-based morphometry. Within the MDD group, further comparisons were performed focusing on the experience of maltreatment during childhood (23 MDD with child abuse vs 11 MDD without child abuse). Compared with healthy controls, the MDD patient group showed decreased GMD in the bilateral orbitofrontal cortices, right superior frontal gyrus, right posterior cingulate gyrus, bilateral middle occipital gyri, and left cuneus. In addition, the patient group showed increased GMD in bilateral postcentral gyri, parieto-occipital cortices, putamina, thalami, and hippocampi, and left cerebellar declive and tuber of vermis. Within the MDD patient group, the subgroup with abuse showed a tendency of decreased GMD in right orbitofrontal cortex, but showed increased GMD in the left postcentral gyrus compared to the subgroup without abuse. Our findings suggest a complicated dysfunction of networks between cortical-subcortical circuits in MDD. In addition, increased GMD in postcentral gyrus and a possible reduction of GMD in the orbitofrontal cortex of MDD patients with abuse subgroup may be associated with abnormalities of body perception and emotional dysregulation.

Cortical and sub-cortical effects in primate models of cocaine use: implications for addiction and the increased risk of psychiatric illness.

PubMed

Bradberry, Charles W

2011-02-01

Drug abuse is a serious risk factor for the incidence and severity of multiple psychiatric illnesses. Understanding the neurobiological consequences of repeated exposure to abused drugs can help to inform how those risks are manifested in terms of specific neurochemical mechanisms and brain networks. This review examines selective studies in non-human primates that employed a cocaine self-administration model. Neurochemical consequences of chronic exposure appear to differ from observations in rodent studies. Whereas chronic intermittent exposure in the rodent is usually associated with a dose-dependent increase in dopaminergic response to a cocaine challenge, in the rhesus monkey, high cumulative exposure was not observed to cause a sensitized dopamine response. These non-human primate observations are concordant with clinical findings in human users. The results of cue exposure studies on dopaminergic transmission are also reviewed. Direct microdialysis measurements indicate that there is not a sustained increase in dopamine associated with cocaine-linked cues. As an alternative to striatal dopaminergic mechanisms mediating cue effects, single unit studies in prefrontal cortex during self-administration in monkeys suggests the orbitofrontal and anterior cingulate cortex are strongly engaged by cocaine cues. Based on the strong clinical imaging literature on cortical and cognitive dysfunction associated with addiction, it is proposed that the strong engagement of cortical systems during repeated cocaine reinforcement results in maladaptive changes that contribute to the risks of drug use for exacerbation of other psychiatric disorders.

Brain pathways for cognitive-emotional decision making in the human animal.

PubMed

Levine, Daniel S

2009-04-01

As roles for different brain regions become clearer, a picture emerges of how primate prefrontal cortex executive circuitry influences subcortical decision making pathways inherited from other mammals. The human's basic needs or drives can be interpreted as residing in an on-center off-surround network in motivational regions of the hypothalamus and brain stem. Such a network has multiple attractors that, in this case, represent the amount of satisfaction of these needs, and we consider and interpret neurally a continuous-time simulated annealing algorithm for moving between attractors under the influence of noise that represents "discontent" combined with "initiative." For decision making on specific tasks, we employ a variety of rules whose neural circuitry appears to involve the amygdala and the orbital, cingulate, and dorsolateral regions of prefrontal cortex. These areas can be interpreted as connected in a three-layer adaptive resonance network. The vigilance of the network, which is influenced by the state of the hypothalamic needs network, determines the level of sophistication of the rule being utilized.

Improving Motor Corticothalamic Communication After Stroke Using Real-Time fMRI Connectivity-Based Neurofeedback.

PubMed

Liew, Sook-Lei; Rana, Mohit; Cornelsen, Sonja; Fortunato de Barros Filho, Marcos; Birbaumer, Niels; Sitaram, Ranganatha; Cohen, Leonardo G; Soekadar, Surjo R

2016-08-01

Two thirds of stroke survivors experience motor impairment resulting in long-term disability. The anatomical substrate is often the disruption of cortico-subcortical pathways. It has been proposed that reestablishment of cortico-subcortical communication relates to functional recovery. In this study, we applied a novel training protocol to augment ipsilesional cortico-subcortical connectivity after stroke. Chronic stroke patients with severe motor impairment were provided online feedback of blood-oxygenation level dependent signal connectivity between cortical and subcortical regions critical for motor function using real-time functional magnetic resonance imaging neurofeedback. In this proof of principle study, 3 out of 4 patients learned to voluntarily modulate cortico-subcortical connectivity as intended. Our results document for the first time the feasibility and safety for patients with chronic stroke and severe motor impairment to self-regulate and augment ipsilesional cortico-subcortical connectivity through neurofeedback using real-time functional magnetic resonance imaging. © The Author(s) 2015.

Certain features of the cochleovestibular syndrome in the residual stage of traumatic brain disease

NASA Technical Reports Server (NTRS)

Garshin, M. I.; Volyanskiy, V. Y.

1980-01-01

Caloric and rotation tests were applied to the study of the vestibular analyser in 84 patients in the residual state of traumatic disease of the brain. Vestibular disturbances of different degree revealed in 79 patients were as a rule accomplished by cochlear derangement. In the majority of patients the vestibular syndrome was supratentorial with the involvement of the diencephal-hypothalmic, subcortical, and cortical levels of the brain. Vestibular dysfunction correlated with such factors as severity of the sustained craniocerebral traum, duration of the posttraumatic period, and, particularly, with the character of the residual neurological syndrome. In accordance with the latter, it is recommended that vestibular disturbances be treated in the residual period of closed craniocerebral injuries with due regard for the principal pathophysiological mechanisms of the underlying neurological syndrome.

The role of the ipsilesional side in the rehabilitation of post-stroke subjects.

PubMed

Silva, Augusta; Sousa, Andreia S P; Silva, Cláudia Costa; Santos, Rubim; Tavares, João Manuel R S; Sousa, Filipa

2017-09-01

Most stroke lesions occur in the middle cerebral artery territory, presenting a high probability of damage of pathways with predominant ipsilesional disposition, mainly related to postural control. Despite the high probability of bilateral postural control dysfunction based on neuroanatomical fundaments, both research and clinical rehabilitation involving stroke subjects have been focused on contralesional side (also named affected side) impairments, while ipsilesional side (also named non-affected side) impairments have been attributed to an adaptive strategy. This paper aims to present a critical understanding about the state-of-the-art that sustains the hypothesis that stroke subjects with middle cerebral artery territory lesion at the subcortical level show an atypical behaviour in the ipsilateral side associated with the lesion itself and the possible implications.

Sex dimorphism in seizure-controlling networks.

PubMed

Giorgi, Fillippo Sean; Galanopoulou, Aristea S; Moshé, Solomon L

2014-12-01

Males and females show a different predisposition to certain types of seizures in clinical studies. Animal studies have provided growing evidence for sexual dimorphism of certain brain regions, including those that control seizures. Seizures are modulated by networks involving subcortical structures, including thalamus, reticular formation nuclei, and structures belonging to the basal ganglia. In animal models, the substantia nigra pars reticulata (SNR) is the best studied of these areas, given its relevant role in the expression and control of seizures throughout development in the rat. Studies with bilateral infusions of the GABA(A) receptor agonist muscimol have identified distinct roles of the anterior or posterior rat SNR in flurothyl seizure control, that follow sex-specific maturational patterns during development. These studies indicate that (a) the regional functional compartmentalization of the SNR appears only after the third week of life, (b) only the male SNR exhibits muscimol-sensitive proconvulsant effects which, in older animals, is confined to the posterior SNR, and (c) the expression of the muscimol-sensitive anticonvulsant effects become apparent earlier in females than in males. The first three postnatal days are crucial in determining the expression of the muscimol-sensitive proconvulsant effects of the immature male SNR, depending on the gonadal hormone setting. Activation of the androgen receptors during this early period seems to be important for the formation of this proconvulsant SNR region. We describe molecular/anatomical candidates underlying these age- and sex-related differences, as derived from in vitro and in vivo experiments, as well as by [(14)C]2-deoxyglucose autoradiography. These involve sex-specific patterns in the developmental changes in the structure or physiology or GABA(A) receptors or of other subcortical structures (e.g., locus coeruleus, hippocampus) that may affect the function of seizure-controlling networks. Copyright © 2014 Elsevier Inc. All rights reserved.

Bilingual Contexts Modulate the Inhibitory Control Network

PubMed Central

Yang, Jing; Ye, Jianqiao; Wang, Ruiming; Zhou, Ke; Wu, Yan Jing

2018-01-01

The present functional magnetic resonance imaging (fMRI) study investigated influences of language contexts on inhibitory control and the underlying neural processes. Thirty Cantonese–Mandarin–English trilingual speakers, who were highly proficient in Cantonese (L1) and Mandarin (L2), and moderately proficient in English (L3), performed a picture-naming task in three dual-language contexts (L1-L2, L2-L3, and L1-L3). After each of the three naming tasks, participants performed a flanker task, measuring contextual effects on the inhibitory control system. Behavioral results showed a typical flanker effect in the L2-L3 and L1-L3 condition, but not in the L1-L2 condition, which indicates contextual facilitation on inhibitory control performance by the L1-L2 context. Whole brain analysis of the fMRI data acquired during the flanker tasks showed more neural activations in the right prefrontal cortex and subcortical areas in the L2-L3 and L1-L3 condition on one hand as compared to the L1-L2 condition on the other hand, suggesting greater involvement of the cognitive control areas when participants were performing the flanker task in L2-L3 and L1-L3 contexts. Effective connectivity analyses displayed a cortical-subcortical-cerebellar circuitry for inhibitory control in the trilinguals. However, contrary to the right-lateralized network in the L1-L2 condition, functional networks for inhibitory control in the L2-L3 and L1-L3 condition are less integrated and more left-lateralized. These findings provide a novel perspective for investigating the interaction between bilingualism (multilingualism) and inhibitory control by demonstrating instant behavioral effects and neural plasticity as a function of changes in global language contexts. PMID:29636713

Bilingual Contexts Modulate the Inhibitory Control Network.

PubMed

Yang, Jing; Ye, Jianqiao; Wang, Ruiming; Zhou, Ke; Wu, Yan Jing

2018-01-01

The present functional magnetic resonance imaging (fMRI) study investigated influences of language contexts on inhibitory control and the underlying neural processes. Thirty Cantonese-Mandarin-English trilingual speakers, who were highly proficient in Cantonese (L1) and Mandarin (L2), and moderately proficient in English (L3), performed a picture-naming task in three dual-language contexts (L1-L2, L2-L3, and L1-L3). After each of the three naming tasks, participants performed a flanker task, measuring contextual effects on the inhibitory control system. Behavioral results showed a typical flanker effect in the L2-L3 and L1-L3 condition, but not in the L1-L2 condition, which indicates contextual facilitation on inhibitory control performance by the L1-L2 context. Whole brain analysis of the fMRI data acquired during the flanker tasks showed more neural activations in the right prefrontal cortex and subcortical areas in the L2-L3 and L1-L3 condition on one hand as compared to the L1-L2 condition on the other hand, suggesting greater involvement of the cognitive control areas when participants were performing the flanker task in L2-L3 and L1-L3 contexts. Effective connectivity analyses displayed a cortical-subcortical-cerebellar circuitry for inhibitory control in the trilinguals. However, contrary to the right-lateralized network in the L1-L2 condition, functional networks for inhibitory control in the L2-L3 and L1-L3 condition are less integrated and more left-lateralized. These findings provide a novel perspective for investigating the interaction between bilingualism (multilingualism) and inhibitory control by demonstrating instant behavioral effects and neural plasticity as a function of changes in global language contexts.

Beamformer source analysis and connectivity on concurrent EEG and MEG data during voluntary movements.

PubMed

Muthuraman, Muthuraman; Hellriegel, Helge; Hoogenboom, Nienke; Anwar, Abdul Rauf; Mideksa, Kidist Gebremariam; Krause, Holger; Schnitzler, Alfons; Deuschl, Günther; Raethjen, Jan

2014-01-01

Electroencephalography (EEG) and magnetoencephalography (MEG) are the two modalities for measuring neuronal dynamics at a millisecond temporal resolution. Different source analysis methods, to locate the dipoles in the brain from which these dynamics originate, have been readily applied to both modalities alone. However, direct comparisons and possible advantages of combining both modalities have rarely been assessed during voluntary movements using coherent source analysis. In the present study, the cortical and sub-cortical network of coherent sources at the finger tapping task frequency (2-4 Hz) and the modes of interaction within this network were analysed in 15 healthy subjects using a beamformer approach called the dynamic imaging of coherent sources (DICS) with subsequent source signal reconstruction and renormalized partial directed coherence analysis (RPDC). MEG and EEG data were recorded simultaneously allowing the comparison of each of the modalities separately to that of the combined approach. We found the identified network of coherent sources for the finger tapping task as described in earlier studies when using only the MEG or combined MEG+EEG whereas the EEG data alone failed to detect single sub-cortical sources. The signal-to-noise ratio (SNR) level of the coherent rhythmic activity at the tapping frequency in MEG and combined MEG+EEG data was significantly higher than EEG alone. The functional connectivity analysis revealed that the combined approach had more active connections compared to either of the modalities during the finger tapping (FT) task. These results indicate that MEG is superior in the detection of deep coherent sources and that the SNR seems to be more vital than the sensitivity to theoretical dipole orientation and the volume conduction effect in the case of EEG.

Beamformer Source Analysis and Connectivity on Concurrent EEG and MEG Data during Voluntary Movements

PubMed Central

Muthuraman, Muthuraman; Hellriegel, Helge; Hoogenboom, Nienke; Anwar, Abdul Rauf; Mideksa, Kidist Gebremariam; Krause, Holger; Schnitzler, Alfons; Deuschl, Günther; Raethjen, Jan

2014-01-01

Electroencephalography (EEG) and magnetoencephalography (MEG) are the two modalities for measuring neuronal dynamics at a millisecond temporal resolution. Different source analysis methods, to locate the dipoles in the brain from which these dynamics originate, have been readily applied to both modalities alone. However, direct comparisons and possible advantages of combining both modalities have rarely been assessed during voluntary movements using coherent source analysis. In the present study, the cortical and sub-cortical network of coherent sources at the finger tapping task frequency (2–4 Hz) and the modes of interaction within this network were analysed in 15 healthy subjects using a beamformer approach called the dynamic imaging of coherent sources (DICS) with subsequent source signal reconstruction and renormalized partial directed coherence analysis (RPDC). MEG and EEG data were recorded simultaneously allowing the comparison of each of the modalities separately to that of the combined approach. We found the identified network of coherent sources for the finger tapping task as described in earlier studies when using only the MEG or combined MEG+EEG whereas the EEG data alone failed to detect single sub-cortical sources. The signal-to-noise ratio (SNR) level of the coherent rhythmic activity at the tapping frequency in MEG and combined MEG+EEG data was significantly higher than EEG alone. The functional connectivity analysis revealed that the combined approach had more active connections compared to either of the modalities during the finger tapping (FT) task. These results indicate that MEG is superior in the detection of deep coherent sources and that the SNR seems to be more vital than the sensitivity to theoretical dipole orientation and the volume conduction effect in the case of EEG. PMID:24618596

Resting state brain networks in the prairie vole.

PubMed

Ortiz, Juan J; Portillo, Wendy; Paredes, Raul G; Young, Larry J; Alcauter, Sarael

2018-01-19

Resting state functional magnetic resonance imaging (rsfMRI) has shown the hierarchical organization of the human brain into large-scale complex networks, referred as resting state networks. This technique has turned into a promising translational research tool after the finding of similar resting state networks in non-human primates, rodents and other animal models of great value for neuroscience. Here, we demonstrate and characterize the presence of resting states networks in Microtus ochrogaster, the prairie vole, an extraordinary animal model to study complex human-like social behavior, with potential implications for the research of normal social development, addiction and neuropsychiatric disorders. Independent component analysis of rsfMRI data from isoflurane-anestethized prairie voles resulted in cortical and subcortical networks, including primary motor and sensory networks, but also included putative salience and default mode networks. We further discuss how future research could help to close the gap between the properties of the large scale functional organization and the underlying neurobiology of several aspects of social cognition. These results contribute to the evidence of preserved resting state brain networks across species and provide the foundations to explore the use of rsfMRI in the prairie vole for basic and translational research.

Apathy in Parkinson's Disease: An Electrophysiological Study

PubMed Central

Mathis, Stéphane; Neau, Jean-Philippe; Pluchon, Claudette; Fargeau, Marie-Noëlle; Karolewicz, Stéphane; Iljicsov, Anna; Gil, Roger

2014-01-01

In Parkinson's disease (PD), apathy (or loss of motivation) is frequent. Nevertheless, the contribution of attentional disorders to its genesis is still not clearly known. We want to determine the relation existing between apathy and attentional disorders by using P300a (or novelty P3) as a marker of the attentional process. The study included 25 patients (13 women and 12 men) with PD for whom we have determined the relationship between automatic attention (represented by P300a) and motor status, apathy, executive dysfunction, mental flexibility, inhibitory control, and depression/anxiety. We have found a correlation between the apathy score and amplitude of novelty P300 during the ON period and also a correlation of the apathy score with a decrease in amplitude of P300 during the OFF period. In a linear regression model, changes in the P300a predicted the severity of apathy independently of any other variable. We concluded firstly that the reduction in amplitude of the P300a wave was a neurophysiological marker of apathy in PD and secondly that apathy led to both dopaminergic denervation (mesolimbic) and nondopaminergic (dorsolateral prefrontal-subcortical) dysfunction. PMID:24804097

Adaptive neuroplastic responses in early and late hemispherectomized monkeys.

PubMed

Burke, Mark W; Kupers, Ron; Ptito, Maurice

2012-01-01

Behavioural recovery in children who undergo medically required hemispherectomy showcase the remarkable ability of the cerebral cortex to adapt and reorganize following insult early in life. Case study data suggest that lesions sustained early in childhood lead to better recovery compared to those that occur later in life. In these children, it is possible that neural reorganization had begun prior to surgery but was masked by the dysfunctional hemisphere. The degree of neural reorganization has been difficult to study systematically in human infants. Here we present a 20-year culmination of data on our nonhuman primate model (Chlorocebus sabeus) of early-life hemispherectomy in which behavioral recovery is interpreted in light of plastic processes that lead to the anatomical reorganization of the early-damaged brain. The model presented here suggests that significant functional recovery occurs after the removal of one hemisphere in monkeys with no preexisting neurological dysfunctions. Human and primate studies suggest a critical role for subcortical and brainstem structures as well as corticospinal tracts in the neuroanatomical reorganization which result in the remarkable behavioral recovery following hemispherectomy. The non-human primate model presented here offers a unique opportunity for studying the behavioral and functional neuroanatomical reorganization that underlies developmental plasticity.

Large-Scale Brain Systems in ADHD: Beyond the Prefrontal-Striatal Model

PubMed Central

Castellanos, F. Xavier; Proal, Erika

2012-01-01

Attention-deficit/hyperactivity disorder (ADHD) has long been thought to reflect dysfunction of prefrontal-striatal circuitry, with involvement of other circuits largely ignored. Recent advances in systems neuroscience-based approaches to brain dysfunction enable the development of models of ADHD pathophysiology that encompass a number of different large-scale “resting state” networks. Here we review progress in delineating large-scale neural systems and illustrate their relevance to ADHD. We relate frontoparietal, dorsal attentional, motor, visual, and default networks to the ADHD functional and structural literature. Insights emerging from mapping intrinsic brain connectivity networks provide a potentially mechanistic framework for understanding aspects of ADHD, such as neuropsychological and behavioral inconsistency, and the possible role of primary visual cortex in attentional dysfunction in the disorder. PMID:22169776

Face Patch Resting State Networks Link Face Processing to Social Cognition

PubMed Central

Schwiedrzik, Caspar M.; Zarco, Wilbert; Everling, Stefan; Freiwald, Winrich A.

2015-01-01

Faces transmit a wealth of social information. How this information is exchanged between face-processing centers and brain areas supporting social cognition remains largely unclear. Here we identify these routes using resting state functional magnetic resonance imaging in macaque monkeys. We find that face areas functionally connect to specific regions within frontal, temporal, and parietal cortices, as well as subcortical structures supporting emotive, mnemonic, and cognitive functions. This establishes the existence of an extended face-recognition system in the macaque. Furthermore, the face patch resting state networks and the default mode network in monkeys show a pattern of overlap akin to that between the social brain and the default mode network in humans: this overlap specifically includes the posterior superior temporal sulcus, medial parietal, and dorsomedial prefrontal cortex, areas supporting high-level social cognition in humans. Together, these results reveal the embedding of face areas into larger brain networks and suggest that the resting state networks of the face patch system offer a new, easily accessible venue into the functional organization of the social brain and into the evolution of possibly uniquely human social skills. PMID:26348613

Irregular behavior in an excitatory-inhibitory neuronal network

NASA Astrophysics Data System (ADS)

Park, Choongseok; Terman, David

2010-06-01

Excitatory-inhibitory networks arise in many regions throughout the central nervous system and display complex spatiotemporal firing patterns. These neuronal activity patterns (of individual neurons and/or the whole network) are closely related to the functional status of the system and differ between normal and pathological states. For example, neurons within the basal ganglia, a group of subcortical nuclei that are responsible for the generation of movement, display a variety of dynamic behaviors such as correlated oscillatory activity and irregular, uncorrelated spiking. Neither the origins of these firing patterns nor the mechanisms that underlie the patterns are well understood. We consider a biophysical model of an excitatory-inhibitory network in the basal ganglia and explore how specific biophysical properties of the network contribute to the generation of irregular spiking. We use geometric dynamical systems and singular perturbation methods to systematically reduce the model to a simpler set of equations, which is suitable for analysis. The results specify the dependence on the strengths of synaptic connections and the intrinsic firing properties of the cells in the irregular regime when applied to the subthalamopallidal network of the basal ganglia.

Lesions of the Medial Striatum in Monkeys Produce Perseverative Impairments during Reversal Learning Similar to Those Produced by Lesions of the Orbitofrontal Cortex

PubMed Central

Clarke, Hannah F.; Robbins, Trevor W.; Roberts, Angela C.

2014-01-01

The ability to switch responding between two visual stimuli based on their changing relationship with reward is dependent on the orbitofrontal cortex (OFC). OFC lesions in humans, monkeys, and rats disrupt performance on a common test of this ability, the visual serial discrimination reversal task. This finding is of particular significance to our understanding of psychiatric disorders such as obsessive–compulsive disorder (OCD) and schizophrenia, in which behavioral inflexibility is a prominent symptom. Although OFC dysfunction can occur in these disorders, there is considerable evidence for more widespread dysfunction within frontostriatal and frontoamygdalar circuitry. Because the contribution of these subcortical structures to behavioral flexibility is poorly understood, the present study compared the effects of excitotoxic lesions of the medial striatum (MS), amygdala, and OFC in the marmoset monkey on performance of the serial reversal task. All monkeys were able to learn a novel stimulus–reward association but, compared with both control and amygdala-lesioned monkeys, those with MS or OFC lesions showed a perseverative impairment in their ability to reverse this association. However, whereas both MS and OFC groups showed insensitivity to negative feedback, only OFC-lesioned monkeys showed insensitivity to positive feedback. These findings suggest that, for different reasons, both the MS and OFC support behavioral flexibility after changes in reward contingencies, and are consistent with the hypothesis that striatal and OFC dysfunction can contribute to pathological perseveration. PMID:18945905

Blood-brain barrier dysfunction and cerebral small vessel disease (arteriolosclerosis) in brains of older people.

PubMed

Bridges, Leslie R; Andoh, Joycelyn; Lawrence, Andrew J; Khoong, Cheryl H L; Poon, Wayne; Esiri, Margaret M; Markus, Hugh S; Hainsworth, Atticus H

2014-11-01

The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis, and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains with minimal Alzheimer disease pathology (Braak Stages 0-II) (n = 84; aged 65 years or older). Morphometric measures of fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with fibrinogen and immunoglobulin G was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001). Fibrinogen in DGM showed a modest association with a history of hypertension; DWM fibrinogen was associated with dementia and cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with leukoaraiosis identified in life (p < 0.05), but fibrinogen was not. Our data suggest that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.

Decreased subcortical volumes in alcohol dependent individuals: effect of polysubstance use disorder.

PubMed

Grodin, Erica N; Momenan, Reza

2017-09-01

Chronic alcohol use has widespread effects on brain morphometry. Alcohol dependent individuals are often diagnosed with comorbid substance use disorders. Alterations in brain morphometry may be different in individuals that are dependent on alcohol alone and individuals dependent on alcohol and other substances. We examined subcortical brain volumes in 37 individuals with alcohol dependence only (ADO), 37 individuals with polysubstance use disorder (PS) and 37 healthy control participants (HC). Participants underwent a structural MR scan and a model-based segmentation tool was used to measure the volume of 14 subcortical regions (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens). Compared to HC, ADO had smaller volume in the bilateral hippocampus, right nucleus accumbens and right thalamus. PS only had volume reductions in the bilateral thalamus compared to HC. PS had a larger right caudate compared to ADO. Subcortical volume was negatively associated with drinking measures only in the ADO group. This study confirms the association between alcohol dependence and reductions in subcortical brain volume. It also suggests that polysubstance use interacts with alcohol use to produce limited subcortical volume reduction and at least one region of subcortical volume increase. These findings indicate that additional substance use may mask damage through inflammation or may function in a protective manner, shielding subcortical regions from alcohol-induced damage. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

The Episodic Memory System: Neurocircuitry and Disorders

PubMed Central

Dickerson, Bradford C; Eichenbaum, Howard

2010-01-01

The ability to encode and retrieve our daily personal experiences, called episodic memory, is supported by the circuitry of the medial temporal lobe (MTL), including the hippocampus, which interacts extensively with a number of specific distributed cortical and subcortical structures. In both animals and humans, evidence from anatomical, neuropsychological, and physiological studies indicates that cortical components of this system have key functions in several aspects of perception and cognition, whereas the MTL structures mediate the organization and persistence of the network of memories whose details are stored in those cortical areas. Structures within the MTL, and particularly the hippocampus, have distinct functions in combining information from multiple cortical streams, supporting our ability to encode and retrieve details of events that compose episodic memories. Conversely, selective damage in the hippocampus, MTL, and other structures of the large-scale memory system, or deterioration of these areas in several diseases and disorders, compromises episodic memory. A growing body of evidence is converging on a functional organization of the cortical, subcortical, and MTL structures that support the fundamental features of episodic memory in humans and animals. PMID:19776728

Reward processing in neurodegenerative disease

PubMed Central

Perry, David C.; Kramer, Joel H.

2015-01-01

Representation of reward value involves a distributed network including cortical and subcortical structures. Because neurodegenerative illnesses target specific anatomic networks that partially overlap with the reward circuit they would be predicted to have distinct impairments in reward processing. This review presents the existing evidence of reward processing changes in neurodegenerative diseases including mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease, as well as in healthy aging. Carefully distinguishing the different aspects of reward processing (primary rewards, secondary rewards, reward-based learning, and reward-based decision-making) and using tasks that differentiate the stages of processing reward will lead to improved understanding of this fundamental process and clarify a contributing cause of behavioral change in these illnesses. PMID:24417286

[Anesthesia and Consciousness].

PubMed

Ogino, Yuichi; Kawamichi, Hiroaki; Saiot, Shigeru

2016-05-01

The mechanism of consciousness and loss of conciousness by general anesthetics are crucial issue for the anesthesiologists. Recent non-invasive brain-imaging technology brings about light to various our emotions and sensations in human brain; however, neural correlate of consciousness is not yet still elucidated. The concept "the seat of the consciousness (is in the subcortical nuclei)" is now completely denied, but instead the consciousness is based on the idea that connectivity and communications across cortical and thalamocortical networks. Anesthetics and sleep disrupt the networks that encompass complexity and integration. The compatibility between complexity and integration is the key feature of the consciousness, which is represented by complex, extensive, communicative and integrative electroencephalograph currents evoked by transcranial magnetic stimulation, provoking a single unified conscious experience in us, humans.

Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex.

PubMed

Yamamuro, Kazuhiko; Yoshino, Hiroki; Ogawa, Yoichi; Makinodan, Manabu; Toritsuka, Michihiro; Yamashita, Masayuki; Corfas, Gabriel; Kishimoto, Toshifumi

2018-03-01

Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown. Since hypomyelination due to isolation is prominent in deep-layer of medial PFC (mPFC), we focused on 2 types of Layer-5 pyramidal cells in the mPFC: prominent h-current (PH) cells and nonprominent h-current (non-PH) cells. We found that a 2-week social isolation after weaning leads to a specific deterioration in action potential properties and reduction in excitatory synaptic inputs in PH cells. The effects of social isolation on PH cells, which involve reduction in functional glutamatergic synapses and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate charge ratio, are specific to the 2 weeks after weaning and to the mPFC. We conclude that juvenile social experience plays crucial roles in the functional development in a subtype of Layer-5 pyramidal cells in the mPFC. Since these neurons project to subcortical structures, a deficit in social experience during the critical period may result in immature neural circuitry between mPFC and subcortical targets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Multi-modal Brain MRI in Subjects with PD and iRBD.

PubMed

Mangia, Silvia; Svatkova, Alena; Mascali, Daniele; Nissi, Mikko J; Burton, Philip C; Bednarik, Petr; Auerbach, Edward J; Giove, Federico; Eberly, Lynn E; Howell, Michael J; Nestrasil, Igor; Tuite, Paul J; Michaeli, Shalom

2017-01-01

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a condition that often evolves into Parkinson's disease (PD). Therefore, by monitoring iRBD it is possible to track the neurodegeneration of individuals who may progress to PD. Here we aimed at piloting the characterization of brain tissue properties in mid-brain subcortical regions of 10 healthy subjects, 8 iRBD, and 9 early-diagnosed PD. We used a battery of magnetic resonance imaging (MRI) contrasts at 3 T, including adiabatic and non-adiabatic rotating frame techniques developed by our group, along with diffusion tensor imaging (DTI) and resting-state fMRI. Adiabatic T 1ρ and T 2ρ , and non-adiabatic RAFF4 (Relaxation Along a Fictitious Field in the rotating frame of rank 4) were found to have lower coefficient of variations and higher sensitivity to detect group differences as compared to DTI parameters such as fractional anisotropy and mean diffusivity. Significantly longer T 1ρ were observed in the amygdala of PD subjects vs. controls, along with a trend of lower functional connectivity as measured by regional homogeneity, thereby supporting the notion that amygdalar dysfunction occurs in PD. Significant abnormalities in reward networks occurred in iRBD subjects, who manifested lower network strength of the accumbens. In agreement with previous studies, significantly longer T 1ρ occurred in the substantia nigra compacta of PD vs. controls, indicative of neuronal degeneration, while regional homogeneity was lower in the substantia nigra reticulata. Finally, other trend-level findings were observed, i.e., lower RAFF4 and T 2ρ in the midbrain of iRBD subjects vs. controls, possibly indicating changes in non-motor features as opposed to motor function in the iRBD group. We conclude that rotating frame relaxation methods along with functional connectivity measures are valuable to characterize iRBD and PD subjects, and with proper validation in larger cohorts may provide pathological signatures of iRBD and PD.

Ultra-high-field fMRI insights on insight: Neural correlates of the Aha!-moment.

PubMed

Tik, Martin; Sladky, Ronald; Luft, Caroline Di Bernardi; Willinger, David; Hoffmann, André; Banissy, Michael J; Bhattacharya, Joydeep; Windischberger, Christian

2018-04-17

Finding creative solutions to difficult problems is a fundamental aspect of human culture and a skill highly needed. However, the exact neural processes underlying creative problem solving remain unclear. Insightful problem solving tasks were shown to be a valid method for investigating one subcomponent of creativity: the Aha!-moment. Finding insightful solutions during a remote associates task (RAT) was found to elicit specific cortical activity changes. Considering the strong affective components of Aha!-moments, as manifested in the subjectively experienced feeling of relief following the sudden emergence of the solution of the problem without any conscious forewarning, we hypothesized the subcortical dopaminergic reward network to be critically engaged during Aha. To investigate those subcortical contributions to insight, we employed ultra-high-field 7 T fMRI during a German Version of the RAT. During this task, subjects were exposed to word triplets and instructed to find a solution word being associated with all the three given words. They were supposed to press a button as soon as they felt confident about their solution without further revision, allowing us to capture the exact event of Aha!-moment. Besides the finding on cortical involvement of the left anterior middle temporal gyrus (aMTG), here we showed for the first time robust subcortical activity changes related to insightful problem solving in the bilateral thalamus, hippocampus, and the dopaminergic midbrain comprising ventral tegmental area (VTA), nucleus accumbens (NAcc), and caudate nucleus. These results shed new light on the affective neural mechanisms underlying insightful problem solving. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats

PubMed Central

Achterberg, E.J. Marijke; van Kerkhof, Linda W.M.; Damsteegt, Ruth; Trezza, Viviana

2015-01-01

Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD. PMID:25568111

Cortical and subcortical mechanisms of brain-machine interfaces.

PubMed

Marchesotti, Silvia; Martuzzi, Roberto; Schurger, Aaron; Blefari, Maria Laura; Del Millán, José R; Bleuler, Hannes; Blanke, Olaf

2017-06-01

Technical advances in the field of Brain-Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole-brain level. Here, we provide a comprehensive and detailed report of the areas active during on-line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG-based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI-actions. Our data revealed an extended cortical-subcortical network involved in operating a motor-imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp 38:2971-2989, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The mouse cortico-striatal projectome

PubMed Central

Hintiryan, Houri; Foster, Nicholas N.; Bowman, Ian; Bay, Maxwell; Song, Monica Y.; Gou, Lin; Yamashita, Seita; Bienkowski, Michael S.; Zingg, Brian; Zhu, Muye; Yang, X. William; Shih, Jean C.; Toga, Arthur W.; Dong, Hong-Wei

2017-01-01

Different cortical areas are organized into distinct intra-cortical subnetworks. How descending pathways from the entire cortex interact subcortically as a network remains unclear. Here, we report an open-access comprehensive mesoscale cortico-striatal projectome—a detailed connectivity projection map from the entire cerebral cortex to the dorsal striatum or caudoputamen (CP) in rodents. Based on these projections, we use novel computational neuroanatomical tools to identify 29 distinct functional striatal domains. Further, we characterize different cortico-striatal networks and how they reconfigure across the rostral-caudal extent of the CP. The workflow was also applied to select cortico-striatal connections in two different mouse models of disconnection syndromes to demonstrate its utility in characterizing circuitry-specific connectopathies. Together, this work provides the structural basis for studying the functional diversity of the dorsal striatum and disruptions of cortico-basal ganglia networks across a broad range of disorders. PMID:27322419

Thalamic structures and associated cognitive functions: Relations with age and aging.

PubMed

Fama, Rosemary; Sullivan, Edith V

2015-07-01

The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive functions known to decline in normal aging, including component processes of memory and executive functions of attention and information processing. The macrostructure, microstructure, and neural connectivity of the thalamus changes across the adult lifespan. Structural and functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural degradation, with anterior regions generally more compromised than posterior regions. The integrity of selective thalamic nuclei and projections decline with advancing age, particularly those in thalamofrontal, thalamoparietal, and thalamolimbic networks. This review presents studies that assess the relations between age and aging and the structure, function, and connectivity of the thalamus and associated neural networks and focuses on their relations with processes of attention, speed of information processing, and working and episodic memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of anesthesia on cerebral blood flow, cerebral metabolic rate, and brain functional connectivity.

PubMed

Bonhomme, Vincent; Boveroux, Pierre; Hans, Pol; Brichant, Jean François; Vanhaudenhuyse, Audrey; Boly, Melanie; Laureys, Steven

2011-10-01

To describe recent studies exploring brain function under the influence of hypnotic anesthetic agents, and their implications on the understanding of consciousness physiology and anesthesia-induced alteration of consciousness. Cerebral cortex is the primary target of the hypnotic effect of anesthetic agents, and higher-order association areas are more sensitive to this effect than lower-order processing regions. Increasing concentration of anesthetic agents progressively attenuates connectivity in the consciousness networks, while connectivity in lower-order sensory and motor networks is preserved. Alteration of thalamic sub-cortical regulation could compromise the cortical integration of information despite preserved thalamic activation by external stimuli. At concentrations producing unresponsiveness, the activity of consciousness networks becomes anticorrelated with thalamic activity, while connectivity in lower-order sensory networks persists, although with cross-modal interaction alterations. Accumulating evidence suggests that hypnotic anesthetic agents disrupt large-scale cerebral connectivity. This would result in an inability of the brain to generate and integrate information, while external sensory information is still processed at a lower order of complexity.

Insula Demonstrates a Non-Linear Response to Varying Demand for Cognitive Control and Weaker Resting Connectivity With the Executive Control Network in Smokers.

PubMed

Fedota, John R; Matous, Allison L; Salmeron, Betty Jo; Gu, Hong; Ross, Thomas J; Stein, Elliot A

2016-09-01

Deficits in cognitive control processes are a primary characteristic of nicotine addiction. However, while network-based connectivity measures of dysfunction have frequently been observed, empirical evidence of task-based dysfunction in these processes has been inconsistent. Here, in a sample of smokers (n=35) and non-smokers (n=21), a previously validated parametric flanker task is employed to characterize addiction-related alterations in responses to varying (ie, high, intermediate, and low) demands for cognitive control. This approach yields a demand-response curve that aims to characterize potential non-linear responses to increased demand for control, including insensitivities or lags in fully activating the cognitive control network. We further used task-based differences in activation between groups as seeds for resting-state analysis of network dysfunction in an effort to more closely link prior inconsistencies in task-related activation with evidence of impaired network connectivity in smokers. For both smokers and non-smokers, neuroimaging results showed similar increases in activation in brain areas associated with cognitive control. However, reduced activation in right insula was seen only in smokers and only when processing intermediate demand for cognitive control. Further, in smokers, this task-modulated right insula showed weaker functional connectivity with the superior frontal gyrus, a component of the task-positive executive control network. These results demonstrate that the neural instantiation of salience attribution in smokers is both more effortful to fully activate and has more difficulty communicating with the exogenous, task-positive, executive control network. Together, these findings further articulate the cognitive control dysfunction associated with smoking and illustrate a specific brain circuit potentially responsible.

Atomoxetine restores the response inhibition network in Parkinson’s disease

PubMed Central

Rae, Charlotte L.; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E.; Jones, P. Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

2016-01-01

Abstract Parkinson’s disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson’s disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson’s disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson’s disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson’s disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson’s disease. PMID:27343257

The Development and Application of the Explanatory Model of School Dysfunctions

ERIC Educational Resources Information Center

Bergman, Manfred Max; Bergman, Zinette; Gravett, Sarah

2011-01-01

This article develops the Explanatory Model of School Dysfunctions based on 80 essays of school principals and their representatives in Gauteng. It reveals the degree and kinds of school dysfunctions, as well as their interconnectedness with actors, networks, and domains. The model provides a basis for theory-based analyses of specific…

Salience Network and Parahippocampal Dopamine Dysfunction in Memory-Impaired Parkinson Disease

PubMed Central

Christopher, Leigh; Duff-Canning, Sarah; Koshimori, Yuko; Segura, Barbara; Boileau, Isabelle; Chen, Robert; Lang, Anthony E.; Houle, Sylvain; Rusjan, Pablo; Strafella, Antonio P.

2016-01-01

Objective Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n=9), PD with nonamnestic MCI (n=10), PD without MCI (n=11), and healthy controls (n=14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction. PMID:25448687

Intrinsic connectivity networks from childhood to late adolescence: Effects of age and sex.

PubMed

Solé-Padullés, Cristina; Castro-Fornieles, Josefina; de la Serna, Elena; Calvo, Rosa; Baeza, Inmaculada; Moya, Jaime; Lázaro, Luisa; Rosa, Mireia; Bargalló, Nuria; Sugranyes, Gisela

2016-02-01

There is limited evidence on the effects of age and sex on intrinsic connectivity of networks underlying cognition during childhood and adolescence. Independent component analysis was conducted in 113 subjects aged 7-18; the default mode, executive control, anterior salience, basal ganglia, language and visuospatial networks were identified. The effect of age was examined with multiple regression, while sex and 'age × sex' interactions were assessed by dividing the sample according to age (7-12 and 13-18 years). As age increased, connectivity in the dorsal and ventral default mode network became more anterior and posterior, respectively, while in the executive control network, connectivity increased within frontoparietal regions. The basal ganglia network showed increased engagement of striatum, thalami and precuneus. The anterior salience network showed greater connectivity in frontal areas and anterior cingulate, and less connectivity of orbitofrontal, middle cingulate and temporoparietal regions. The language network presented increased connectivity of inferior frontal and decreased connectivity within the right middle frontal and left inferior parietal cortices. The visuospatial network showed greater engagement of inferior parietal and frontal cortices. No effect of sex, nor age by sex interactions was observed. These findings provide evidence of strengthening of cortico-cortical and cortico-subcortical networks across childhood and adolescence. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Attention dysfunction of postoperative patients with glioma.

PubMed

Fang, Dazhao; Jiang, Jian; Sun, Xiaoyang; Wang, Weijie; Dong, Nan; Fu, Xianhua; Pang, Cong; Chen, Xingui; Ding, Lianshu

2014-10-15

Attention dysfunction has been observed among many kinds of nervous system diseases, including glioma. This study aimed to investigate the correlation between glioma localization, malignancy, postoperative recovery time and attention deficit. A total of 45 patients with glioma who underwent surgical resection and 18 healthy volunteers were enrolled. The attention network test, digital span test, color trail test II and Stroop test were used to detect the characteristics of attention deficit. Orientation network dysfunction was detected in the parietal lobe tumor group, and execution network deficit was detected in both the frontal and parietal lobe groups, while no significant difference was detected in the temporal lobe group compared to healthy controls. The high-grade glioma group (grade III-IV) exhibited more serious functional impairment than the low-grade group (grade I-II). No significant correlation was observed between postoperative recovery time and attention impairment. High-grade glioma patients suffer more severe attention impairment. In addition, the frontal and parietal lobe glioma patients suffer attention dysfunction in dissimilar manner. These findings will provide important guidance on the care of glioma patients after therapy.

Brain Volume Correlates with Duration of Abstinence from Substance Abuse in a Region-Specific and Substance-Specific Manner.

PubMed

Korponay, Cole; Kosson, David S; Decety, Jean; Kiehl, Kent A; Koenigs, Michael

2017-10-01

Human neuroimaging studies indicate that the loss of brain volume associated with substance abuse may be recovered during abstinence. Subcortical and prefrontal cortical regions involved in reward and decision-making are among the regions most consistently implicated in damage and recovery from substance abuse, but the relative capacities of these different brain regions to recover volume during abstinence remains unclear, and it is unknown whether recovery capacities depend on the substance that was abused. Voxel-based morphometry in a prison inmate sample ( n =107) of long-term abstinent former regular users (FRUs) and former light users (FLUs) of alcohol, cocaine, and/or cannabis. Cross-sectional indicators of volume recovery were operationalized as 1) positive correlation between abstinence duration and volume in FRUs and 2) absence of lower volume in FRUs compared to FLUs. In FRUs of alcohol, abstinence duration positively correlated with volume in subcortical regions (particularly the putamen and amygdala) but not prefrontal regions; lower prefrontal but not subcortical volume was observed in FRUs compared to FLUs. In FRUs of cocaine, abstinence duration positively correlated with volume in both subcortical regions (particularly the nucleus accumbens) and prefrontal regions; lower volume was not observed in either subcortical or prefrontal regions in FRUs. In FRUs of cannabis, abstinence duration positively correlated with subcortical but not prefrontal volume; lower prefrontal but not subcortical volume was observed in FRUs. Subcortical structures displayed indicators of volume recovery across FRUs of all three substances, whereas prefrontal regions displayed indicators of volume recovery only in FRUs of cocaine.

Cortical gray and subcortical white matter associations in Parkinson's disease.

PubMed

Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M; Swavely, Steven; Kong, Lan; Styner, Martin; Huang, Xuemei

2017-01-01

Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Fundamentally Distributed Information Processing Integrates the Motor Network into the Mental Workspace during Mental Rotation.

PubMed

Schlegel, Alexander; Konuthula, Dedeepya; Alexander, Prescott; Blackwood, Ethan; Tse, Peter U

2016-08-01

The manipulation of mental representations in the human brain appears to share similarities with the physical manipulation of real-world objects. In particular, some neuroimaging studies have found increased activity in motor regions during mental rotation, suggesting that mental and physical operations may involve overlapping neural populations. Does the motor network contribute information processing to mental rotation? If so, does it play a similar computational role in both mental and manual rotation, and how does it communicate with the wider network of areas involved in the mental workspace? Here we used multivariate methods and fMRI to study 24 participants as they mentally rotated 3-D objects or manually rotated their hands in one of four directions. We find that information processing related to mental rotations is distributed widely among many cortical and subcortical regions, that the motor network becomes tightly integrated into a wider mental workspace network during mental rotation, and that motor network activity during mental rotation only partially resembles that involved in manual rotation. Additionally, these findings provide evidence that the mental workspace is organized as a distributed core network that dynamically recruits specialized subnetworks for specific tasks as needed.

Impaired Consciousness in Epilepsy

PubMed Central

Blumenfeld, Hal

2013-01-01

Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost making it impossible for the individual to experience or respond. This has huge consequences for safety, productivity, emotional health and quality of life. To prevent impaired consciousness in epilepsy it is necessary to understand the mechanisms leading to brain dysfunction during seizures. Normally the “consciousness system”—a specialized set of cortical-subcortical structures—maintains alertness, attention and awareness. Recent advances in neuroimaging, electrophysiology and prospective behavioral testing have shed new light on how epileptic seizures disrupt the consciousness system. Diverse seizure types including absence, generalized tonic-clonic and complex partial seizures converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding these mechanisms may lead to improved treatment strategies to prevent impaired consciousness and improve quality of life in people with epilepsy. PMID:22898735

Bilingual language processing after a lesion in the left thalamic and temporal regions. A case report with early childhood onset

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Lieshout, P.; Renier, W.; Eling, P.

1990-02-01

This case study concerns an 18-year-old bilingual girl who suffered a radiation lesion in the left (dominant) thalamic and temporal region when she was 4 years old. Language and memory assessment revealed deficits in auditory short-term memory, auditory word comprehension, nonword repetition, syntactic processing, word fluency, and confrontation naming tasks. Both languages (English and Dutch) were found to be affected in a similar manner, despite the fact that one language (English) was acquired before and the other (Dutch) after the period of lesion onset. Most of the deficits appear to be related to verbal (short-term) memory dysfunction. Several hypotheses ofmore » subcortical involvement in memory processes are discussed with reference to existing theories in this area.« less

Identification of a Functional Connectome for Long-Term Fear Memory in Mice

PubMed Central

Wheeler, Anne L.; Teixeira, Cátia M.; Wang, Afra H.; Xiong, Xuejian; Kovacevic, Natasa; Lerch, Jason P.; McIntosh, Anthony R.; Parkinson, John; Frankland, Paul W.

2013-01-01

Long-term memories are thought to depend upon the coordinated activation of a broad network of cortical and subcortical brain regions. However, the distributed nature of this representation has made it challenging to define the neural elements of the memory trace, and lesion and electrophysiological approaches provide only a narrow window into what is appreciated a much more global network. Here we used a global mapping approach to identify networks of brain regions activated following recall of long-term fear memories in mice. Analysis of Fos expression across 84 brain regions allowed us to identify regions that were co-active following memory recall. These analyses revealed that the functional organization of long-term fear memories depends on memory age and is altered in mutant mice that exhibit premature forgetting. Most importantly, these analyses indicate that long-term memory recall engages a network that has a distinct thalamic-hippocampal-cortical signature. This network is concurrently integrated and segregated and therefore has small-world properties, and contains hub-like regions in the prefrontal cortex and thalamus that may play privileged roles in memory expression. PMID:23300432

Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.

PubMed

Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu

2015-05-01

The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.

Neural correlates of consciousness during general anesthesia using functional magnetic resonance imaging (fMRI).

PubMed

Bonhomme, V; Boveroux, P; Brichant, J F; Laureys, S; Boly, M

2012-01-01

This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose function is hierarchically altered in a dose-dependent manner. Higher order networks, thought to be involved in mental content generation, as well as sub-cortical networks involved in thalamic activity regulation seems to be affected first by increasing concentrations of hypnotic agents that enhance inhibitory neurotransmission. Lower order sensory networks are preserved, including thalamo-cortical connectivity into those networks, even at concentrations that suppress responsiveness, but cross-modal sensory interactions are inhibited. Thalamo-cortical connectivity into the consciousness networks decreases with increasing concentrations of those agents, and is transformed into an anti-correlated activity between the thalamus and the cortex for the deepest levels of sedation, when the subject is non responsive. Future will tell us whether these brain function alterations are also observed with hypnotic agents that mainly inhibit excitatory neurotransmission. The link between the observations made using fMRI and the identified biochemical targets of hypnotic anesthetic agents still remains to be identified.

Comparative Study of Subcortical Atrophy in Patients with Frontotemporal Dementia and Dementia with Extrapyramidal Signs

PubMed Central

Caixeta, Leonardo; Vieira, Renata Teles; Paes, Flávia; Carta, Mauro Giovanni; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Rocha, Nuno B. F; Budde, Henning; Machado, Sergio

2015-01-01

Objectives : To investigate the severity of subcortical atrophy in frontotemporal dementia (FTD) without extrapyramidal symptoms (EPS) and dementia with EPS. In addition, we aim to verify if there is correlation between demographic and clinical characteristics and subcortical atrophy in the groups. Methodology : The sample was composed of 21 patients with dementia and EPS as well as 19 patients with FTD without EPS. A linear assessment was conducted in order to identify the degree of subcortical atrophy (i.e., bifrontal index - BFI) using MRI. Moreover, the Mini-Mental State Examination (MMSE), Pfeffer Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating (CDR) were used to investigate clinical aspects. Results : It was verified that patients with dementia and EPS was older than the patients with FTD (p=0.01). The severity of cognitive deficits was associated with BFI, as well as the dementia severity in the EPS group. Conclusion : FTD group presented mean BFI scores above the cutoff for normal elderly population, indicating the presence of subcortical atrophy in this group. Mean BFI was higher (although not statistically significant) in FTD group than in dementia with EPS, which can suggest at least that subcortical pathology in FTD may be as important as in the dementia with EPS group. Subcortical atrophy is a good biological marker for cognitive deterioration in FTD and in dementia with EPS. PMID:25870648

Decreased triple network connectivity in patients with post-traumatic stress disorder

NASA Astrophysics Data System (ADS)

Liu, Yang; Li, Liang; Li, Baojuan; Zhang, Xi; Lu, Hongbing

2017-03-01

The triple network model provides a common framework for understanding affective and neurocognitive dysfunctions across multiple disorders, including central executive network (CEN), default mode network (DMN), and salience network (SN). Considering the effect of traumatic experience on post-traumatic stress disorder (PTSD), this study aims to explore the alteration of triple network connectivity in a specific PTSD induced by a single prolonged trauma exposure. With arterial spin labeling sequence, three networks were identified using independent component analysis in 10 PTSD patients and 10 healthy survivors, who experienced the same coal mining flood disaster. In PTSD patients, decreased connectivity was identified in left middle frontal gyrus of CEN, left precuneus and bilateral superior frontal gyrus of DMN, and right anterior insula of SN. The decreased connectivity in left middle frontal gyrus was identified to associate with clinical severity. These results indicated the decreased triple network connectivity, which not only supported the proposal of the triple network model, but also prompted possible neurobiology mechanism of cognitive dysfunction for this kind of PTSD.

Neurobiological correlates of cognitions in fear and anxiety: a cognitive-neurobiological information-processing model.

PubMed

Hofmann, Stefan G; Ellard, Kristen K; Siegle, Greg J

2012-01-01

We review likely neurobiological substrates of cognitions related to fear and anxiety. Cognitive processes are linked to abnormal early activity reflecting hypervigilance in subcortical networks involving the amygdala, hippocampus, and insular cortex, and later recruitment of cortical regulatory resources, including activation of the anterior cingulate cortex and prefrontal cortex to implement avoidant response strategies. Based on this evidence, we present a cognitive-neurobiological information-processing model of fear and anxiety, linking distinct brain structures to specific stages of information processing of perceived threat.

Theoretical exploration of the neural bases of behavioural disinhibition, apathy and executive dysfunction in preclinical Alzheimer's disease in people with Down's syndrome: potential involvement of multiple frontal-subcortical neuronal circuits.

PubMed

Ball, S L; Holland, A J; Watson, P C; Huppert, F A

2010-04-01

Recent research has suggested a specific impairment in frontal-lobe functioning in the preclinical stages of Alzheimer's disease (AD) in people with Down's syndrome (DS), characterised by prominent changes in personality or behaviour. The aim of the current paper is to explore whether particular kinds of change (namely executive dysfunction (EDF), disinhibition and apathy), associated in the literature with disruption of different underlying frontal-subcortical circuits, are a) more or less frequently reported than others and b) related to poor performance on tasks involving different cognitive processes. Seventy-eight participants (mean age 47 years, range 36-72) with DS and mild to moderate intellectual disability (based on ICD-10 criteria), without a diagnosis of dementia of Alzheimer's type (DAT) or other psychiatric disorders, were selected from a larger sample of older adults with DS (n = 122). Dementia diagnosis was based on the CAMDEX informant interview, conducted with each participant's main carer. Informant-reported changes in personality/behaviour and memory were recorded. Participants were scored based on symptoms falling into three behavioural domains and completed five executive function (EF) tasks, six memory tasks (two of which also had a strong executive component) and the BPVS (as a measure of general intellectual ability). Multiple regression analyses were conducted to determine the degree to which the behavioural variables of 'EDF', 'disinhibition' and 'apathy', along with informant-reported memory decline and antidepressant medication use, predicted performance on the cognitive tasks (whilst controlling for the effects of age and general intellectual ability). Strikingly, disinhibited behaviour was reported for 95.7% of participants with one or more behavioural change (n = 47) compared to 57.4% with reported apathy and 36.2% with reported EDF. 'Disinhibition' score significantly predicted performance on three EF tasks (designed to measure planning, response inhibition and working memory) and an object memory task, (also thought to place high demands on working memory), while 'apathy' score significantly predicted performance on two different tasks, those measuring spatial reversal and prospective memory (p < 0.05). Informant reported memory decline was associated only with performance on a delayed recall task while antidepressant medication use was associated with better performance on a working memory task (p < 0.05). Observed dissociation between performance on cognitive tasks associated with reported apathy and disinhibition is in keeping with proposed differences underlying neural circuitry and supports the involvement of multiple frontal-subcortical circuits in the early stages of DAT in DS. However, the prominence of disinhibition in the behavioural profile (which more closely resembles that of disinhibited subtype of DFT than that of AD in the general population) leads us to postulate that the serotonergically mediated orbitofrontal circuit may be disproportionately affected. A speculative theory is developed regarding the biological basis for observed changes and discussion is focused on how this understanding may aid us in the development of treatments directly targeting underlying abnormalities.

Mapping Subcortical Brain Maturation during Adolescence: Evidence of Hemisphere-and Sex-Specific Longitudinal Changes

ERIC Educational Resources Information Center

Dennison, Meg; Whittle, Sarah; Yücel, Murat; Vijayakumar, Nandita; Kline, Alexandria; Simmons, Julian; Allen, Nicholas B.

2013-01-01

Early to mid-adolescence is an important developmental period for subcortical brain maturation, but longitudinal studies of these neurodevelopmental changes are lacking. The present study acquired repeated magnetic resonance images from 60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in subcortical structure volumes.…

Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity.

PubMed

Kaiser, Roselinde H; Andrews-Hanna, Jessica R; Wager, Tor D; Pizzagalli, Diego A

2015-06-01

Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive. To investigate network dysfunction in MDD through a meta-analysis of rsFC studies. Seed-based voxelwise rsFC studies comparing individuals with MDD with healthy controls (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE) and authors contacted for additional data. Twenty-seven seed-based voxel-wise rsFC data sets from 25 publications (556 individuals with MDD and 518 healthy controls) were included in the meta-analysis. Coordinates of seed regions of interest and between-group effects were extracted. Seeds were categorized into seed-networks by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive or reduced negative connectivity) or hypoconnectivity (increased negative or reduced positive connectivity) with each seed-network. Major depressive disorder was characterized by hypoconnectivity within the frontoparietal network, a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network involved in attending to the external environment. Major depressive disorder was also associated with hyperconnectivity within the default network, a network believed to support internally oriented and self-referential thought, and hyperconnectivity between frontoparietal control systems and regions of the default network. Finally, the MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions. Reduced connectivity within frontoparietal control systems and imbalanced connectivity between control systems and networks involved in internal or external attention may reflect depressive biases toward internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.

Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology.

PubMed

Aouizerate, Bruno; Guehl, Dominique; Cuny, Emmanuel; Rougier, Alain; Bioulac, Bernard; Tignol, Jean; Burbaud, Pierre

2004-02-01

Obsessive-compulsive disorder (OCD) is characterized by repetitive intrusive thoughts and compulsive time-consuming behaviors classified into three to five distinct symptom dimensions including: (1) aggressive/somatic obsessions with checking compulsions; (2) contamination concerns with washing compulsions; (3) symmetry obsessions with counting/ordering compulsions; (4) hoarding obsessions with collecting compulsions; and (5) sexual/religious concerns. Phenomenologically, OCD could be thought of as the irruption of internal signals centered on the erroneous perception that "something is wrong" in a specific situation. This generates severe anxiety, leading to recurrent behaviors aimed at reducing the emotional tension. In this paper, we examine how the abnormalities in brain activity reported in OCD can be interpreted in the light of physiology after consideration of various approaches (phenomenology, neuropsychology, neuroimmunology and neuroimagery) that contribute to proposing the central role of several cortical and subcortical regions, especially the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex (DLPC), the head of the caudate nucleus and the thalamus. The OFC is involved in the significance attributed to the consequences of action, thereby subserving decision-making, whereas the ACC is particularly activated in situations in which there are conflicting options and a high likelihood of making an error. The DLPC plays a critical part in the cognitive processing of relevant information. This cortical information is then integrated by the caudate nucleus, which controls behavioral programs. A dysfunction of these networks at one or several stages will result in the emergence and maintenance of repetitive thoughts and characteristic OCD behavior. Copyright 2004 Elsevier Ltd.

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM.

PubMed

Donnemiller, E; Brenneis, C; Wissel, J; Scherfler, C; Poewe, W; Riccabona, G; Wenning, G K

2000-09-01

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.

Hippocampal coupling with cortical and subcortical structures in the context of memory consolidation.

PubMed

Skelin, Ivan; Kilianski, Scott; McNaughton, Bruce L

2018-04-13

Memory consolidation is a gradual process through which episodic memories become incorporated into long-term 'semantic' representations. It likely involves reactivation of neural activity encoding the recent experience during non-REM sleep. A critical prerequisite for memory consolidation is precise coordination of reactivation events between the hippocampus and cortical/subcortical structures, facilitated by the coupling of local field potential (LFP) oscillations (slow oscillations, sleep spindles and sharp wave/ripples) between these structures. We review the rapidly expanding literature on the qualitative and quantitative aspects of hippocampal oscillatory and neuronal coupling with cortical/subcortical structures in the context of memory reactivation. Reactivation in the hippocampus and cortical/subcortical structures is tightly coupled with sharp wave/ripples. Hippocampal-cortical/subcortical coupling is rich in dimensionality and this dimensionality is likely underestimated due to the limitations of the current methodology. Copyright © 2018 Elsevier Inc. All rights reserved.

White Matter Hyperintensities and Hypobaric Exposure

PubMed Central

McGuire, Stephen A.; Sherman, Paul M.; Wijtenburg, S. Andrea; Rowland, Laura M.; Grogan, Patrick M.; Sladky, John H.; Robinson, Andrew Y.; Kochunov, Peter V.

2014-01-01

Objective Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery magnetic resonance imaging (MRI). Methods Eighty-three altitude chamber personnel (PHY), 105 U-2 pilots (U2P), and 148 age- controlled and health-matched doctorate degree controls (DOC) underwent high-resolution MRI. Subcortical WMH burden was quantified as count and volume of subcortical WMH lesions after transformation of images to the Talairach atlas–based stereo-tactic frame. Results Subcortical WMHs were more prevalent in PHY (volume p = 0.011/count p = 0.019) and U2P (volume p<0.001/count p<0.001) when compared to DOC, whereas PHY were not significantly different than U2P. Interpretation This study provides strong evidence that nonhypoxic hypobaric exposure may induce subcortical WMHs in a young, healthy population lacking other risk factors for WMHs and adds this occupational exposure to other environmentally related potential causes of WMHs. PMID:25164539

Subcortical functional reorganization due to early blindness

PubMed Central

Jiang, Fang; Fine, Ione; Watkins, Kate E.; Bridge, Holly

2015-01-01

Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a “visual” subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. PMID:25673746

Subcortical functional reorganization due to early blindness.

PubMed

Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly

2015-04-01

Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.

An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans

PubMed Central

Clasen, Liv; Giedd, Jay N.; Blumenthal, Jonathan; Lerch, Jason P.; Chakravarty, M. Mallar; Raznahan, Armin

2016-01-01

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. SIGNIFICANCE STATEMENT Sex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover, regional brain allometry (nonlinear scaling) poses largely unaddressed methodological and theoretical challenges for such research. We build the first set of allometric norms for global and regional subcortical anatomy, and use these to dissect out the complex, distributed and topologically organized patterns of areal contraction and expansion, which characterize sex and SCD effects on subcortical anatomy. Our data inform basic research into the patterning of neuroanatomical variation, and the clinical neuroscience of sex-chromosome aneuploidy. PMID:26911691

EEG-based functional networks evoked by acupuncture at ST 36: A data-driven thresholding study

NASA Astrophysics Data System (ADS)

Li, Huiyan; Wang, Jiang; Yi, Guosheng; Deng, Bin; Zhou, Hexi

2017-10-01

This paper investigates how acupuncture at ST 36 modulates the brain functional network. 20 channel EEG signals from 15 healthy subjects are respectively recorded before, during and after acupuncture. The correlation between two EEG channels is calculated by using Pearson’s coefficient. A data-driven approach is applied to determine the threshold, which is performed by considering the connected set, connected edge and network connectivity. Based on such thresholding approach, the functional network in each acupuncture period is built with graph theory, and the associated functional connectivity is determined. We show that acupuncturing at ST 36 increases the connectivity of the EEG-based functional network, especially for the long distance ones between two hemispheres. The properties of the functional network in five EEG sub-bands are also characterized. It is found that the delta and gamma bands are affected more obviously by acupuncture than the other sub-bands. These findings highlight the modulatory effects of acupuncture on the EEG-based functional connectivity, which is helpful for us to understand how it participates in the cortical or subcortical activities. Further, the data-driven threshold provides an alternative approach to infer the functional connectivity under other physiological conditions.

Network integrity of the parental brain in infancy supports the development of children's social competencies.

PubMed

Abraham, Eyal; Hendler, Talma; Zagoory-Sharon, Orna; Feldman, Ruth

2016-11-01

The cross-generational transmission of mammalian sociality, initiated by the parent's postpartum brain plasticity and species-typical behavior that buttress offspring's socialization, has not been studied in humans. In this longitudinal study, we measured brain response of 45 primary-caregiving parents to their infant's stimuli, observed parent-infant interactions, and assayed parental oxytocin (OT). Intra- and inter-network connectivity were computed in three main networks of the human parental brain: core limbic, embodied simulation and mentalizing. During preschool, two key child social competencies were observed: emotion regulation and socialization. Parent's network integrity in infancy predicted preschoolers' social outcomes, with subcortical and cortical network integrity foreshadowing simple evolutionary-based regulatory tactics vs complex self-regulatory strategies and advanced socialization. Parent-infant synchrony mediated the links between connectivity of the parent's embodied simulation network and preschoolers' ability to use cognitive/executive emotion regulation strategies, highlighting the inherently dyadic nature of this network and its long-term effects on tuning young to social life. Parent's inter-network core limbic-embodied simulation connectivity predicted children's OT as moderated by parental OT. Findings challenge solipsistic neuroscience perspectives by demonstrating how the parent-offspring interface enables the brain of one human to profoundly impact long-term adaptation of another. © The Author (2016). Published by Oxford University Press.

Spontaneous eyelid closures link vigilance fluctuation with fMRI dynamic connectivity states

PubMed Central

Wang, Chenhao; Ong, Ju Lynn; Patanaik, Amiya; Chee, Michael W. L.

2016-01-01

Fluctuations in resting-state functional connectivity occur but their behavioral significance remains unclear, largely because correlating behavioral state with dynamic functional connectivity states (DCS) engages probes that disrupt the very behavioral state we seek to observe. Observing spontaneous eyelid closures following sleep deprivation permits nonintrusive arousal monitoring. During periods of low arousal dominated by eyelid closures, sliding-window correlation analysis uncovered a DCS associated with reduced within-network functional connectivity of default mode and dorsal/ventral attention networks, as well as reduced anticorrelation between these networks. Conversely, during periods when participants’ eyelids were wide open, a second DCS was associated with less decoupling between the visual network and higher-order cognitive networks that included dorsal/ventral attention and default mode networks. In subcortical structures, eyelid closures were associated with increased connectivity between the striatum and thalamus with the ventral attention network, and greater anticorrelation with the dorsal attention network. When applied to task-based fMRI data, these two DCS predicted interindividual differences in frequency of behavioral lapsing and intraindividual temporal fluctuations in response speed. These findings with participants who underwent a night of total sleep deprivation were replicated in an independent dataset involving partially sleep-deprived participants. Fluctuations in functional connectivity thus appear to be clearly associated with changes in arousal. PMID:27512040

Network integrity of the parental brain in infancy supports the development of children’s social competencies

PubMed Central

Abraham, Eyal; Hendler, Talma; Zagoory-Sharon, Orna

2016-01-01

The cross-generational transmission of mammalian sociality, initiated by the parent’s postpartum brain plasticity and species-typical behavior that buttress offspring’s socialization, has not been studied in humans. In this longitudinal study, we measured brain response of 45 primary-caregiving parents to their infant’s stimuli, observed parent–infant interactions, and assayed parental oxytocin (OT). Intra- and inter-network connectivity were computed in three main networks of the human parental brain: core limbic, embodied simulation and mentalizing. During preschool, two key child social competencies were observed: emotion regulation and socialization. Parent’s network integrity in infancy predicted preschoolers’ social outcomes, with subcortical and cortical network integrity foreshadowing simple evolutionary-based regulatory tactics vs complex self-regulatory strategies and advanced socialization. Parent–infant synchrony mediated the links between connectivity of the parent’s embodied simulation network and preschoolers' ability to use cognitive/executive emotion regulation strategies, highlighting the inherently dyadic nature of this network and its long-term effects on tuning young to social life. Parent’s inter-network core limbic-embodied simulation connectivity predicted children’s OT as moderated by parental OT. Findings challenge solipsistic neuroscience perspectives by demonstrating how the parent–offspring interface enables the brain of one human to profoundly impact long-term adaptation of another. PMID:27369068

Why would Musical Training Benefit the Neural Encoding of Speech? The OPERA Hypothesis.

PubMed

Patel, Aniruddh D

2011-01-01

Mounting evidence suggests that musical training benefits the neural encoding of speech. This paper offers a hypothesis specifying why such benefits occur. The "OPERA" hypothesis proposes that such benefits are driven by adaptive plasticity in speech-processing networks, and that this plasticity occurs when five conditions are met. These are: (1) Overlap: there is anatomical overlap in the brain networks that process an acoustic feature used in both music and speech (e.g., waveform periodicity, amplitude envelope), (2) Precision: music places higher demands on these shared networks than does speech, in terms of the precision of processing, (3) Emotion: the musical activities that engage this network elicit strong positive emotion, (4) Repetition: the musical activities that engage this network are frequently repeated, and (5) Attention: the musical activities that engage this network are associated with focused attention. According to the OPERA hypothesis, when these conditions are met neural plasticity drives the networks in question to function with higher precision than needed for ordinary speech communication. Yet since speech shares these networks with music, speech processing benefits. The OPERA hypothesis is used to account for the observed superior subcortical encoding of speech in musically trained individuals, and to suggest mechanisms by which musical training might improve linguistic reading abilities.

Community structure in networks of functional connectivity: resolving functional organization in the rat brain with pharmacological MRI.

PubMed

Schwarz, Adam J; Gozzi, Alessandro; Bifone, Angelo

2009-08-01

In the study of functional connectivity, fMRI data can be represented mathematically as a network of nodes and links, where image voxels represent the nodes and the connections between them reflect a degree of correlation or similarity in their response. Here we show that, within this framework, functional imaging data can be partitioned into 'communities' of tightly interconnected voxels corresponding to maximum modularity within the overall network. We evaluated this approach systematically in application to networks constructed from pharmacological MRI (phMRI) of the rat brain in response to acute challenge with three different compounds with distinct mechanisms of action (d-amphetamine, fluoxetine, and nicotine) as well as vehicle (physiological saline). This approach resulted in bilaterally symmetric sub-networks corresponding to meaningful anatomical and functional connectivity pathways consistent with the purported mechanism of action of each drug. Interestingly, common features across all three networks revealed two groups of tightly coupled brain structures that responded as functional units independent of the specific neurotransmitter systems stimulated by the drug challenge, including a network involving the prefrontal cortex and sub-cortical regions extending from the striatum to the amygdala. This finding suggests that each of these networks includes general underlying features of the functional organization of the rat brain.

Cerebral serotonin transporter binding is inversely related to body mass index.

PubMed

Erritzoe, D; Frokjaer, V G; Haahr, M T; Kalbitzer, J; Svarer, C; Holst, K K; Hansen, D L; Jernigan, T L; Lehel, S; Knudsen, G M

2010-08-01

Overweight and obesity is a health threat of increasing concern and understanding the neurobiology behind obesity is instrumental to the development of effective treatment regimes. Serotonergic neurotransmission is critically involved in eating behaviour; cerebral level of serotonin (5-HT) in animal models is inversely related to food intake and body weight and some effective anti-obesity agents involve blockade of the serotonin transporter (SERT). We investigated in 60 healthy volunteers body mass index (BMI) and regional cerebral SERT binding as measured with [(11)C]DASB PET. In a linear regression model with adjustment for relevant covariates, we found that cortical and subcortical SERT binding was negatively correlated to BMI (-0.003 to -0.012 BP(ND) unit per kg/m(2)). Tobacco smoking and alcohol consumption did not affect cerebral SERT binding. Several effective anti-obesity drugs encompass blockade of the SERT; yet, our study is the first to demonstrate an abnormally decreased cerebral SERT binding in obese individuals. Whether the SERT has a direct role in the regulation of appetite and eating behaviour or whether the finding is due to a compensatory downregulation of SERT secondary to other dysfunction(s) in the serotonergic transmitter system, such as low baseline serotonin levels, remains to be established. Copyright 2010 Elsevier Inc. All rights reserved.

Neurologic manifestations in welders with pallidal MRI T1 hyperintensity.

PubMed

Josephs, K A; Ahlskog, J E; Klos, K J; Kumar, N; Fealey, R D; Trenerry, M R; Cowl, C T

2005-06-28

Neurologic symptoms have been attributed to manganese fumes generated during welding. Increased T1 MRI signal in the basal ganglia is a biologic marker of manganese accumulation. Recent studies have associated welding and parkinsonism, but generally without MRI corroboration. To characterize the clinical and neuropsychological features of patients with MRI basal ganglia T1 hyperintensity, who were ultimately diagnosed with neurotoxicity from welding fumes. The medical records of welders referred to the Department of Neurology with neurologic problems and basal ganglia T1 hyperintensity were reviewed. All eight patients were male career welders with increased T1 basal ganglia signal on MRI of the brain. Several different clinical syndromes were recognized: a parkinsonian syndrome (three patients), a syndrome of multifocal myoclonus and limited cognitive impairment (two patients), a mixed syndrome with vestibular-auditory dysfunction (two patients), and minor subjective cognitive impairment, anxiety, and sleep apnea (one patient). Neuropsychometric testing suggested subcortical or frontal involvement. Inadequate ventilation or lack of personal respiratory protection during welding was a common theme. Welding without proper protection was associated with syndromes of parkinsonism, multifocal myoclonus, mild cognitive impairment, and vestibular-auditory dysfunction. The MRI T1 hyperintensity in the basal ganglia suggests that these may have been caused by manganese neurotoxicity.

Subcortical shape and volume abnormalities in an elderly HIV+ cohort

NASA Astrophysics Data System (ADS)

Wade, Benjamin S. C.; Valcour, Victor; Busovaca, Edgar; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Wang, Yalin; Thompson, Paul M.

2015-03-01

Over 50% of HIV+ individuals show significant impairment in psychomotor functioning, processing speed, working memory and attention [1, 2]. Patients receiving combination antiretroviral therapy may still have subcortical atrophy, but the profile of HIV-associated brain changes is poorly understood. With parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ subjects (4 female; age=65.35 ± 2.21) and 31 uninfected elderly controls (2 female; age=64.68 ± 4.57) scanned with MRI as part of a San Francisco Bay Area study of elderly people with HIV. We also investigated whether morphometry was associated with nadir CD4+ (T-cell) counts, viral load and illness duration among HIV+ participants. FreeSurfer was used to segment the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, accumbens, brainstem, callosum and ventricles from brain MRI scans. To study subcortical shape, we analyzed: (1) the Jacobian determinant (JD) indexed over structures' surface coordinates and (2) radial distances (RD) of structure surfaces from a medial curve. A JD less than 1 reflects regional tissue atrophy and greater than 1 reflects expansion. The volumes of several subcortical regions were found to be associated with HIV status. No regional volumes showed detectable associations with CD4 counts, viral load or illness duration. The shapes of numerous subcortical regions were significantly linked to HIV status, detectability of viral RNA and illness duration. Our results show subcortical brain differences in HIV+ subjects in both shape and volumetric domains.

Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder.

PubMed

Konrad, Kerstin; Eickhoff, Simon B

2010-06-01

In recent years, a change in perspective in etiological models of attention deficit hyperactivity disorder (ADHD) has occurred in concordance with emerging concepts in other neuropsychiatric disorders such as schizophrenia and autism. These models shift the focus of the assumed pathology from regional brain abnormalities to dysfunction in distributed network organization. In the current contribution, we report findings from functional connectivity studies during resting and task states, as well as from studies on structural connectivity using diffusion tensor imaging, in subjects with ADHD. Although major methodological limitations in analyzing connectivity measures derived from noninvasive in vivo neuroimaging still exist, there is convergent evidence for white matter pathology and disrupted anatomical connectivity in ADHD. In addition, dysfunctional connectivity during rest and during cognitive tasks has been demonstrated. However, the causality between disturbed white matter architecture and cortical dysfunction remains to be evaluated. Both genetic and environmental factors might contribute to disruptions in interactions between different brain regions. Stimulant medication not only modulates regionally specific activation strength but also normalizes dysfunctional connectivity, pointing to a predominant network dysfunction in ADHD. By combining a longitudinal approach with a systems perspective in ADHD in the future, it might be possible to identify at which stage during development disruptions in neural networks emerge and to delineate possible new endophenotypes of ADHD. (c) 2010 Wiley-Liss, Inc.

An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson’s Disease

PubMed Central

ZGALJARDIC, DENNIS J.; BOROD, JOAN C.; FOLDI, NANCY S.; MATTIS, PAUL J.; GORDON, MARK F.; FEIGIN, ANDREW; EIDELBERG, DAVID

2015-01-01

Parkinson’s disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson’s disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function. PMID:16840240

Has an Angel Shown the Way? Etiological and Therapeutic Implications of the PCP/NMDA Model of Schizophrenia

PubMed Central

Javitt, Daniel C.

2012-01-01

Over the last 20 years, glutamatergic models of schizophrenia have become increasingly accepted as etiopathological models of schizophrenia, based on the observation that phencyclidine (PCP) induces a schizophrenia-like psychosis by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors. This article reviews developments in two key predictions of the model: first, that neurocognitive deficits in schizophrenia should follow the pattern of deficit predicted based on underlying NMDAR dysfunction and, second, that agents that stimulate NMDAR function should be therapeutically beneficial. As opposed to dopamine receptors, NMDAR are widely distributed throughout the brain, including subcortical as well as cortical brain regions, and sensory as well as association cortex. Studies over the past 20 years have documented severe sensory dysfunction in schizophrenia using behavioral, neurophysiological, and functional brain imaging approaches, including impaired generation of key sensory-related potentials such as mismatch negativity and visual P1 potentials. Similar deficits are observed in humans following administration of NMDAR antagonists such as ketamine in either humans or animal models. Sensory dysfunction, in turn, predicts impairments in higher order cognitive functions such as auditory or visual emotion recognition. Treatment studies have been performed with compounds acting directly at the NMDAR glycine site, such as glycine, D-serine, or D-cycloserine, and, more recently, with high-affinity glycine transport inhibitors such as RG1678 (Roche). More limited studies have been performed with compounds targeting the redox site. Overall, these compounds have been found to induce significant beneficial effects on persistent symptoms, suggesting novel approaches for treatment and prevention of schizophrenia. PMID:22987851

Comparison of Brain Activity Correlating with Self-Report versus Narrative Attachment Measures during Conscious Appraisal of an Attachment Figure

PubMed Central

Yaseen, Zimri S.; Zhang, Xian; Muran, J. Christopher; Winston, Arnold; Galynker, Igor I.

2016-01-01

Objectives: The Adult Attachment Interview (AAI) has been the gold standard of attachment assessment, but requires special training. The Relationship Scales Questionnaire (RSQ) is a widely used self-report measure. We investigate how each correlates with brain activity during appraisal of subjects’ mothers. Methods: Twenty-eight women were scored on the AAI, RSQ, and mood measures. During functional magnetic resonance imaging, subjects viewed their mothers in neutral-, valence-, and salience-rating conditions. We identified regions where contrasts in brain activity between appraisal and neutral viewing conditions correlated with each measure of attachment after covarying for mood. AAI and RSQ measures were then compared in terms of the extent to which regions of correlating brain activity overlapped with “default mode network” (DMN) vs. executive frontal network (EFN) masks and cortical vs. subcortical masks. Additionally, interactions with mood were examined. Results: Salience and valence processing associated with increased thalamo-striatal, posterior cingulate, and visual cortex activity. Salience processing decreased PFC activity, whereas valence processing increased left insula activity. Activity correlating with AAI vs. RSQ measures demonstrated significantly more DMN and subcortical involvement. Interactions with mood were observed in the middle temporal gyrus and precuneus for both measures. Conclusion: The AAI appears to disproportionately correlate with conscious appraisal associated activity in DMN and subcortical structures, while the RSQ appears to tap EFN structures more extensively. Thus, the AAI may assess more interoceptive, ‘core-self’-related processes, while the RSQ captures higher-order cognitions involved in attachment. Shared interaction effects between mood and AAI and RSQ-measures may suggest that processes tapped by each belong to a common system. PMID:27014022

The retrosplenial cortex: A memory gateway between the cortical default mode network and the medial temporal lobe.

PubMed

Kaboodvand, Neda; Bäckman, Lars; Nyberg, Lars; Salami, Alireza

2018-05-01

The default mode network (DMN) involves interacting cortical areas, including the posterior cingulate cortex (PCC) and the retrosplenial cortex (RSC), and subcortical areas, including the medial temporal lobe (MTL). The degree of functional connectivity (FC) within the DMN, particularly between MTL and medial-parietal subsystems, relates to episodic memory (EM) processes. However, past resting-state studies investigating the link between posterior DMN-MTL FC and EM performance yielded inconsistent results, possibly reflecting heterogeneity in the degree of connectivity between MTL and specific cortical DMN regions. Animal work suggests that RSC has structural connections to both cortical DMN regions and MTL, and may thus serve as an intermediate layer that facilitates information transfer between cortical and subcortical DMNs. We studied 180 healthy old adults (aged 64-68 years), who underwent comprehensive assessment of EM, along with resting-state fMRI. We found greater FC between MTL and RSC than between MTL and the other cortical DMN regions (e.g., PCC), with the only significant association with EM observed for MTL-RSC FC. Mediational analysis showed that MTL-cortical DMN connectivity increased with RSC as a mediator. Further analysis using a graph-theoretical approach on DMN nodes revealed the highest betweenness centrality for RSC, confirming that a high proportion of short paths among DMN regions pass through RSC. Importantly, the degree of RSC mediation was associated with EM performance, suggesting that individuals with greater mediation have an EM advantage. These findings suggest that RSC forms a critical gateway between MTL and cortical DMN to support EM in older adults. © 2018 Wiley Periodicals, Inc.

Large-scale network dysfunction in Major Depressive Disorder: Meta-analysis of resting-state functional connectivity

PubMed Central

Kaiser, Roselinde H.; Andrews-Hanna, Jessica R.; Wager, Tor D.; Pizzagalli, Diego A.

2015-01-01

IMPORTANCE Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive. OBJECTIVE To investigate network dysfunction in MDD through the first meta-analysis of rsFC studies. DATA SOURCES Seed-based voxel-wise rsFC studies comparing MDD with healthy individuals (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web-of-Science, EMBASE), and authors contacted for additional data. STUDY SELECTION Twenty-seven datasets from 25 publications (556 MDD adults/teens; 518 controls) were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS Coordinates of seed regions-of-interest and between-group effects were extracted. Seeds were categorized into “seed-networks” by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive, or reduced negative, connectivity) or hypoconnectivity (increased negative, or reduced positive, connectivity) with each seed-network. RESULTS MDD was characterized by hypoconnectivity within the frontoparietal network (FN), a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network (DAN) involved in attending to the external environment. MDD was also associated with hyperconnectivity within the default network (DN), a network believed to support internally-oriented and self-referential thought, and hyperconnectivity between FN control systems and regions of DN. Finally, MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions. CONCLUSIONS AND RELEVANCE Reduced connectivity within frontoparietal control systems, and imbalanced connectivity between control systems and networks involved in internal- or external-attention, may reflect depressive biases towards internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression. PMID:25785575

A new combined surface and volume registration

NASA Astrophysics Data System (ADS)

Lepore, Natasha; Joshi, Anand A.; Leahy, Richard M.; Brun, Caroline; Chou, Yi-Yu; Pennec, Xavier; Lee, Agatha D.; Barysheva, Marina; De Zubicaray, Greig I.; Wright, Margaret J.; McMahon, Katie L.; Toga, Arthur W.; Thompson, Paul M.

2010-03-01

3D registration of brain MRI data is vital for many medical imaging applications. However, purely intensitybased approaches for inter-subject matching of brain structure are generally inaccurate in cortical regions, due to the highly complex network of sulci and gyri, which vary widely across subjects. Here we combine a surfacebased cortical registration with a 3D fluid one for the first time, enabling precise matching of cortical folds, but allowing large deformations in the enclosed brain volume, which guarantee diffeomorphisms. This greatly improves the matching of anatomy in cortical areas. The cortices are segmented and registered with the software Freesurfer. The deformation field is initially extended to the full 3D brain volume using a 3D harmonic mapping that preserves the matching between cortical surfaces. Finally, these deformation fields are used to initialize a 3D Riemannian fluid registration algorithm, that improves the alignment of subcortical brain regions. We validate this method on an MRI dataset from 92 healthy adult twins. Results are compared to those based on volumetric registration without surface constraints; the resulting mean templates resolve consistent anatomical features both subcortically and at the cortex, suggesting that the approach is well-suited for cross-subject integration of functional and anatomic data.

REM sleep respiratory behaviours mental content in narcoleptic lucid dreamers.

PubMed

Oudiette, Delphine; Dodet, Pauline; Ledard, Nahema; Artru, Emilie; Rachidi, Inès; Similowski, Thomas; Arnulf, Isabelle

2018-02-08

Breathing is irregular during rapid eye-movement (REM) sleep, whereas it is stable during non-REM sleep. Why this is so remains a mystery. We propose that irregular breathing has a cortical origin and reflects the mental content of dreams, which often accompany REM sleep. We tested 21 patients with narcolepsy who had the exceptional ability to lucid dream in REM sleep, a condition in which one is conscious of dreaming during the dream and can signal lucidity with an ocular code. Sleep and respiration were monitored during multiple naps. Participants were instructed to modify their dream scenario so that it involved vocalizations or an apnoea, -two behaviours that require a cortical control of ventilation when executed during wakefulness. Most participants (86%) were able to signal lucidity in at least one nap. In 50% of the lucid naps, we found a clear congruence between the dream report (e.g., diving under water) and the observed respiratory behaviour (e.g., central apnoea) and, in several cases, a preparatory breath before the respiratory behaviour. This suggests that the cortico-subcortical networks involved in voluntary respiratory movements are preserved during REM sleep and that breathing irregularities during this stage have a cortical/subcortical origin that reflects dream content.

Update on Vascular Cognitive Impairment Associated with Subcortical Small-Vessel Disease

PubMed Central

Wallin, Anders; Román, Gustavo C.; Esiri, Margaret; Kettunen, Petronella; Svensson, Johan; Paraskevas, George P.; Kapaki, Elisabeth

2018-01-01

Subcortical small-vessel disease (SSVD) is a disorder well characterized from the clinical, imaging, and neuropathological viewpoints. SSVD is considered the most prevalent ischemic brain disorder, increasing in frequency with age. Vascular risk factors include hypertension, diabetes, hyperlipidemia, elevated homocysteine, and obstructive sleep apnea. Ischemic white matter lesions are the hallmark of SSVD; other pathological lesions include arteriolosclerosis, dilatation of perivascular spaces, venous collagenosis, cerebral amyloid angiopathy, microbleeds, microinfarcts, lacunes, and large infarcts. The pathogenesis of SSVD is incompletely understood but includes endothelial changes and blood-brain barrier alterations involving metalloproteinases, vascular endothelial growth factors, angiotensin II, mindin/spondin, and the mammalian target of rapamycin pathway. Metabolic and genetic conditions may also play a role but hitherto there are few conclusive studies. Clinical diagnosis of SSVD includes early executive dysfunction manifested by impaired capacity to use complex information, to formulate strategies, and to exercise self-control. In comparison with Alzheimer’s disease (AD), patients with SSVD show less pronounced episodic memory deficits. Brain imaging has advanced substantially the diagnostic tools for SSVD. With the exception of cortical microinfarcts, all other lesions are well visualized with MRI. Diagnostic biomarkers that separate AD from SSVD include reduction of cerebrospinal fluid amyloid-β (Aβ)42 and of the ratio Aβ42/Aβ40 often with increased total tau levels. However, better markers of small-vessel function of intracerebral blood vessels are needed. The treatment of SSVD remains unsatisfactory other than control of vascular risk factors. There is an urgent need of finding targets to slow down and potentially halt the progression of this prevalent, but often unrecognized, disorder. PMID:29562536

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment.

PubMed

Peters, Sarah K; Dunlop, Katharine; Downar, Jonathan

2016-01-01

The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network's associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN's cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders.

Segregation of Brain Structural Networks Supports Spatio-Temporal Predictive Processing.

PubMed

Ciullo, Valentina; Vecchio, Daniela; Gili, Tommaso; Spalletta, Gianfranco; Piras, Federica

2018-01-01

The ability to generate probabilistic expectancies regarding when and where sensory stimuli will occur, is critical to derive timely and accurate inferences about updating contexts. However, the existence of specialized neural networks for inferring predictive relationships between events is still debated. Using graph theoretical analysis applied to structural connectivity data, we tested the extent of brain connectivity properties associated with spatio-temporal predictive performance across 29 healthy subjects. Participants detected visual targets appearing at one out of three locations after one out of three intervals; expectations about stimulus location (spatial condition) or onset (temporal condition) were induced by valid or invalid symbolic cues. Connectivity matrices and centrality/segregation measures, expressing the relative importance of, and the local interactions among specific cerebral areas respect to the behavior under investigation, were calculated from whole-brain tractography and cortico-subcortical parcellation. Results: Response preparedness to cued stimuli relied on different structural connectivity networks for the temporal and spatial domains. Significant covariance was observed between centrality measures of regions within a subcortical-fronto-parietal-occipital network -comprising the left putamen, the right caudate nucleus, the left frontal operculum, the right inferior parietal cortex, the right paracentral lobule and the right superior occipital cortex-, and the ability to respond after a short cue-target delay suggesting that the local connectedness of such nodes plays a central role when the source of temporal expectation is explicit. When the potential for functional segregation was tested, we found highly clustered structural connectivity across the right superior, the left middle inferior frontal gyrus and the left caudate nucleus as related to explicit temporal orienting. Conversely, when the interaction between explicit and implicit temporal orienting processes was considered at the long interval, we found that explicit processes were related to centrality measures of the bilateral inferior parietal lobule. Degree centrality of the same region in the left hemisphere covaried with behavioral measures indexing the process of attentional re-orienting. These results represent a crucial step forward the ordinary predictive processing description, as we identified the patterns of connectivity characterizing the brain organization associated with the ability to generate and update temporal expectancies in case of contextual violations.

Frequency-specific alterations in functional connectivity in treatment-resistant and -sensitive major depressive disorder.

PubMed

He, Zongling; Cui, Qian; Zheng, Junjie; Duan, Xujun; Pang, Yajing; Gao, Qing; Han, Shaoqiang; Long, Zhiliang; Wang, Yifeng; Li, Jiao; Wang, Xiao; Zhao, Jingping; Chen, Huafu

2016-11-01

Major depressive disorder (MDD) may involve alterations in brain functional connectivity in multiple neural circuits and present large-scale network dysfunction. Patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) show different responses to antidepressants and aberrant brain functions. This study aims to investigate functional connectivity patterns of TRD and TSD at the whole brain resting state. Seventeen patients with TRD, 17 patients with TSD, and 17 healthy controls matched with age, gender, and years of education were recruited in this study. The brain was divided using an automated anatomical labeling atlas into 90 regions of interest, which were used to construct the entire brain functional networks. An analysis method called network-based statistic was used to explore the dysconnected subnetworks of TRD and TSD at different frequency bands. At resting state, TSD and TRD present characteristic patterns of network dysfunction at special frequency bands. The dysconnected subnetwork of TSD mainly lies in the fronto-parietal top-down control network. Moreover, the abnormal neural circuits of TRD are extensive and complex. These circuits not only depend on the abnormal affective network but also involve other networks, including salience network, auditory network, visual network, and language processing cortex. Our findings reflect that the pathological mechanism of TSD may refer to impairment in cognitive control, whereas TRD mainly triggers the dysfunction of emotion processing and affective cognition. This study reveals that differences in brain functional connectivity at resting state reflect distinct pathophysiological mechanisms in TSD and TRD. These findings may be helpful in differentiating two types of MDD and predicting treatment responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mediodorsal thalamus and cognition in non-human primates

PubMed Central

Baxter, Mark G.

2013-01-01

Several recent studies in non-human primates have provided new insights into the role of the medial thalamus in different aspects of cognitive function. The mediodorsal nucleus of the thalamus (MD), by virtue of its connectivity with the frontal cortex, has been implicated in an array of cognitive functions. Rather than serving as an engine or relay for the prefrontal cortex, this area seems to be more specifically involved in regulating plasticity and flexibility of prefrontal-dependent cognitive functions. Focal damage to MD may also exacerbate the effects of damage to other subcortical relays. Thus, a wide range of distributed circuits and cognitive functions may be disrupted from focal damage within the medial thalamus (for example as a consequence of stroke or brain injury). Conversely, this region may make an interesting target for neuromodulation of cognitive function via deep brain stimulation or related methods, in conditions associated with dysfunction of these neural circuits. PMID:23964206

Mediodorsal thalamus and cognition in non-human primates.

PubMed

Baxter, Mark G

2013-01-01

Several recent studies in non-human primates have provided new insights into the role of the medial thalamus in different aspects of cognitive function. The mediodorsal nucleus of the thalamus (MD), by virtue of its connectivity with the frontal cortex, has been implicated in an array of cognitive functions. Rather than serving as an engine or relay for the prefrontal cortex, this area seems to be more specifically involved in regulating plasticity and flexibility of prefrontal-dependent cognitive functions. Focal damage to MD may also exacerbate the effects of damage to other subcortical relays. Thus, a wide range of distributed circuits and cognitive functions may be disrupted from focal damage within the medial thalamus (for example as a consequence of stroke or brain injury). Conversely, this region may make an interesting target for neuromodulation of cognitive function via deep brain stimulation or related methods, in conditions associated with dysfunction of these neural circuits.

Schizophrenia in childhood and adolescence.

PubMed

Mala, Eva

2008-12-01

Schizophrenia is a disorder characterized by delay in neurodevelopment and by a central disorder of recognition (i.e. with generalized cognitive deficit). Connectivity impairments in the areas of the social brain and cerebellum are the "messenger" of abnormal CNS development in schizophrenia. Processes of neuronal reorganization in cortical and subcortical structures, aberrant forms of pruning, sprouting, and myelinization may play a major role in the pathogenesis of a schizophrenic breakdown. Models of neuroplasticity during adolescence can be connected with models of neurodevelopmental vulnerability and models of neurotoxicity to form an integrated approach in order to better understand premorbid adjustment, onset, and course of schizophrenia. The loss of plasticity and aberrant myelinization lead to a deterioration in cognitive functions, social dysfunction and, in individuals with specific genetic vulnerability, to expression of schizophrenia. This article discusses brain development in relation to the diagnosis of schizophrenia and the basic symptoms of childhood schizophrenia (with early and very early onset) and of adolescent schizophrenia.

A diffusion modelling approach to understanding contextual cueing effects in children with ADHD

PubMed Central

Weigard, Alexander; Huang-Pollock, Cynthia

2014-01-01

Background Strong theoretical models suggest implicit learning deficits may exist among children with Attention Deficit Hyperactivity Disorder (ADHD). Method We examine implicit contextual cueing (CC) effects among children with ADHD (n=72) and non-ADHD Controls (n=36). Results Using Ratcliff’s drift diffusion model, we found that among Controls, the CC effect is due to improvements in attentional guidance and to reductions in response threshold. Children with ADHD did not show a CC effect; although they were able to use implicitly acquired information to deploy attentional focus, they had more difficulty adjusting their response thresholds. Conclusions Improvements in attentional guidance and reductions in response threshold together underlie the CC effect. Results are consistent with neurocognitive models of ADHD that posit sub-cortical dysfunction but intact spatial attention, and encourage the use of alternative data analytic methods when dealing with reaction time data. PMID:24798140

Sexual risk-taking and subcortical brain volume in adolescence.

PubMed

Feldstein Ewing, Sarah W; Hudson, Karen A; Caouette, Justin; Mayer, Andrew R; Thayer, Rachel E; Ryman, Sephira G; Bryan, Angela D

2018-04-19

The developmental period of adolescence marks the initiation of new socioemotional and physical behaviors, including sexual intercourse. However, little is known about neurodevelopmental influences on adolescent sexual decision-making. We sought to determine how subcortical brain volume correlated with condom use, and whether those associations differed by gender and pubertal development. We used FreeSurfer to extract subcortical volume among N = 169 sexually experienced youth (mean age 16.07 years; 31.95% female). We conducted multiple linear regressions to examine the relationship between frequency of condom use and subcortical volume, and whether these associations would be moderated by gender and pubertal development. We found that the relationship between brain volume and condom use was better accounted for by pubertal development than by gender, and moderated the association between limbic brain volume and condom use. No significant relationships were observed in reward areas (e.g., nucleus accumbens) or prefrontal cortical control areas. These data highlight the potential relevance of subcortical socioemotional processing structures in adolescents' sexual decision-making.

Age-related differences in the structural complexity of subcortical and ventricular structures.

PubMed

Madan, Christopher R; Kensinger, Elizabeth A

2017-02-01

It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18-94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

A Computational Model of Major Depression: the Role of Glutamate Dysfunction on Cingulo-Frontal Network Dynamics

PubMed Central

Ramirez-Mahaluf, Juan P.; Roxin, Alexander; Mayberg, Helen S.; Compte, Albert

2017-01-01

Abstract Major depression disease (MDD) is associated with the dysfunction of multinode brain networks. However, converging evidence implicates the reciprocal interaction between midline limbic regions (typified by the ventral anterior cingulate cortex, vACC) and the dorso-lateral prefrontal cortex (dlPFC), reflecting interactions between emotions and cognition. Furthermore, growing evidence suggests a role for abnormal glutamate metabolism in the vACC, while serotonergic treatments (selective serotonin reuptake inhibitor, SSRI) effective for many patients implicate the serotonin system. Currently, no mechanistic framework describes how network dynamics, glutamate, and serotonin interact to explain MDD symptoms and treatments. Here, we built a biophysical computational model of 2 areas (vACC and dlPFC) that can switch between emotional and cognitive processing. MDD networks were simulated by slowing glutamate decay in vACC and demonstrated sustained vACC activation. This hyperactivity was not suppressed by concurrent dlPFC activation and interfered with expected dlPFC responses to cognitive signals, mimicking cognitive dysfunction seen in MDD. Simulation of clinical treatments (SSRI or deep brain stimulation) counteracted this aberrant vACC activity. Theta and beta/gamma oscillations correlated with network function, representing markers of switch-like operation in the network. The model shows how glutamate dysregulation can cause aberrant brain dynamics, respond to treatments, and be reflected in EEG rhythms as biomarkers of MDD. PMID:26514163

Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features

PubMed Central

Mahoney, Colin J.; Beck, Jon; Rohrer, Jonathan D.; Lashley, Tammaryn; Mok, Kin; Shakespeare, Tim; Yeatman, Tom; Warrington, Elizabeth K.; Schott, Jonathan M.; Fox, Nick C.; Rossor, Martin N.; Hardy, John; Collinge, John; Revesz, Tamas; Mead, Simon

2012-01-01

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43–68 years) and duration (1.7–22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration–TAR DNA-binding protein. These findings corroborate the clinical importance of the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic and neuropathological features that could help to guide genetic testing, and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network. PMID:22366791

Audiovisual integration in hemianopia: A neurocomputational account based on cortico-collicular interaction.

PubMed

Magosso, Elisa; Bertini, Caterina; Cuppini, Cristiano; Ursino, Mauro

2016-10-01

Hemianopic patients retain some abilities to integrate audiovisual stimuli in the blind hemifield, showing both modulation of visual perception by auditory stimuli and modulation of auditory perception by visual stimuli. Indeed, conscious detection of a visual target in the blind hemifield can be improved by a spatially coincident auditory stimulus (auditory enhancement of visual detection), while a visual stimulus in the blind hemifield can improve localization of a spatially coincident auditory stimulus (visual enhancement of auditory localization). To gain more insight into the neural mechanisms underlying these two perceptual phenomena, we propose a neural network model including areas of neurons representing the retina, primary visual cortex (V1), extrastriate visual cortex, auditory cortex and the Superior Colliculus (SC). The visual and auditory modalities in the network interact via both direct cortical-cortical connections and subcortical-cortical connections involving the SC; the latter, in particular, integrates visual and auditory information and projects back to the cortices. Hemianopic patients were simulated by unilaterally lesioning V1, and preserving spared islands of V1 tissue within the lesion, to analyze the role of residual V1 neurons in mediating audiovisual integration. The network is able to reproduce the audiovisual phenomena in hemianopic patients, linking perceptions to neural activations, and disentangles the individual contribution of specific neural circuits and areas via sensitivity analyses. The study suggests i) a common key role of SC-cortical connections in mediating the two audiovisual phenomena; ii) a different role of visual cortices in the two phenomena: auditory enhancement of conscious visual detection being conditional on surviving V1 islands, while visual enhancement of auditory localization persisting even after complete V1 damage. The present study may contribute to advance understanding of the audiovisual dialogue between cortical and subcortical structures in healthy and unisensory deficit conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pedunculopontine network dysfunction in Parkinson's disease with postural control and sleep disorders.

PubMed

Gallea, Cecile; Ewenczyk, Claire; Degos, Bertrand; Welter, Marie-Laure; Grabli, David; Leu-Semenescu, Smaranda; Valabregue, Romain; Berroir, Pierre; Yahia-Cherif, Lydia; Bertasi, Eric; Fernandez-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Benali, Habib; Poupon, Cyril; François, Chantal; Arnulf, Isabelle; Lehéricy, Stéphane; Vidailhet, Marie

2017-05-01

The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Amino Acid Neurotransmitters; Mechanisms of Their Uptake into Synaptic Vesicles

DTIC Science & Technology

1991-08-01

4.1.1.15), is localized in specific GABAergic nerve terminals (Fonnum et al, 1970). The subcortical telencephalon , which contains among others the...ratio between the vesicular uptake of GABA and glycine is similar in cerebral cortex, subcortical telencephalon , whole brain, and spinal cord. This is...regions, cerebral cortex, cerebellum, medulla and subcortical telencephalon (i.e. forebrain after removal of cortex). The vesicular uptake is low and

Intraoperative Subcortical Fiber Mapping with Subcortico-Cortical Evoked Potentials.

PubMed

Enatsu, Rei; Kanno, Aya; Ohtaki, Shunya; Akiyama, Yukinori; Ochi, Satoko; Mikuni, Nobuhiro

2016-02-01

During brain surgery, there are difficulties associated with identifying subcortical fibers with no clear landmarks. We evaluated the usefulness of cortical evoked potentials with subcortical stimuli (subcortico-cortical evoked potential [SCEP]) in identifying subcortical fibers intraoperatively. We used SCEP to identify the pyramidal tract in 4 patients, arcuate fasciculus in 1 patient, and both in 2 patients during surgical procedures. After resection, a 1 × 4-electrode plate was placed on the floor of the removal cavity and 1-Hz alternating electrical stimuli were delivered to this electrode. A 4 × 5 recording electrode plate was placed on the central cortical areas to map the pyramidal tract and temporoparietal cortical areas for the arcuate fasciculus. SCEPs were obtained by averaging electrocorticograms time locked to the stimulus onset. The subcortical stimulation within 15 mm of the target fiber induced cortical evoked potentials in the corresponding areas, whereas the stimulation apart from 20 mm did not. Five patients showed transient worsening of neurologic symptoms after surgery. However, all patients recovered. SCEP was useful for identifying subcortical fibers and confirmed the preservation of these fibers. This technique is expected to contribute to the effectiveness and safety of resective surgery in patients with lesions close to eloquent areas. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationships between structure, in vivo function and long-range axonal target of cortical pyramidal tract neurons.

PubMed

Rojas-Piloni, Gerardo; Guest, Jason M; Egger, Robert; Johnson, Andrew S; Sakmann, Bert; Oberlaender, Marcel

2017-10-11

Pyramidal tract neurons (PTs) represent the major output cell type of the neocortex. To investigate principles of how the results of cortical processing are broadcasted to different downstream targets thus requires experimental approaches, which provide access to the in vivo electrophysiology of PTs, whose subcortical target regions are identified. On the example of rat barrel cortex (vS1), we illustrate that retrograde tracer injections into multiple subcortical structures allow identifying the long-range axonal targets of individual in vivo recorded PTs. Here we report that soma depth and dendritic path lengths within each cortical layer of vS1, as well as spiking patterns during both periods of ongoing activity and during sensory stimulation, reflect the respective subcortical target regions of PTs. We show that these cellular properties result in a structure-function parameter space that allows predicting a PT's subcortical target region, without the need to inject multiple retrograde tracers.The major output cell type of the neocortex - pyramidal tract neurons (PTs) - send axonal projections to various subcortical areas. Here the authors combined in vivo recordings, retrograde tracings, and reconstructions of PTs in rat somatosensory cortex to show that PT structure and activity can predict specific subcortical targets.

Tau burden and the functional connectome in Alzheimer's disease and progressive supranuclear palsy.

PubMed

Cope, Thomas E; Rittman, Timothy; Borchert, Robin J; Jones, P Simon; Vatansever, Deniz; Allinson, Kieren; Passamonti, Luca; Vazquez Rodriguez, Patricia; Bevan-Jones, W Richard; O'Brien, John T; Rowe, James B

2018-02-01

Alzheimer's disease and progressive supranuclear palsy (PSP) represent neurodegenerative tauopathies with predominantly cortical versus subcortical disease burden. In Alzheimer's disease, neuropathology and atrophy preferentially affect 'hub' brain regions that are densely connected. It was unclear whether hubs are differentially affected by neurodegeneration because they are more likely to receive pathological proteins that propagate trans-neuronally, in a prion-like manner, or whether they are selectively vulnerable due to a lack of local trophic factors, higher metabolic demands, or differential gene expression. We assessed the relationship between tau burden and brain functional connectivity, by combining in vivo PET imaging using the ligand AV-1451, and graph theoretic measures of resting state functional MRI in 17 patients with Alzheimer's disease, 17 patients with PSP, and 12 controls. Strongly connected nodes displayed more tau pathology in Alzheimer's disease, independently of intrinsic connectivity network, validating the predictions of theories of trans-neuronal spread but not supporting a role for metabolic demands or deficient trophic support in tau accumulation. This was not a compensatory phenomenon, as the functional consequence of increasing tau burden in Alzheimer's disease was a progressive weakening of the connectivity of these same nodes, reducing weighted degree and local efficiency and resulting in weaker 'small-world' properties. Conversely, in PSP, unlike in Alzheimer's disease, those nodes that accrued pathological tau were those that displayed graph metric properties associated with increased metabolic demand and a lack of trophic support rather than strong functional connectivity. Together, these findings go some way towards explaining why Alzheimer's disease affects large scale connectivity networks throughout cortex while neuropathology in PSP is concentrated in a small number of subcortical structures. Further, we demonstrate that in PSP increasing tau burden in midbrain and deep nuclei was associated with strengthened cortico-cortical functional connectivity. Disrupted cortico-subcortical and cortico-brainstem interactions meant that information transfer took less direct paths, passing through a larger number of cortical nodes, reducing closeness centrality and eigenvector centrality in PSP, while increasing weighted degree, clustering, betweenness centrality and local efficiency. Our results have wide-ranging implications, from the validation of models of tau trafficking in humans to understanding the relationship between regional tau burden and brain functional reorganization. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain.

Chronic spatial working memory deficit associated with the superior longitudinal fasciculus: a study using voxel-based lesion-symptom mapping and intraoperative direct stimulation in right prefrontal glioma surgery.

PubMed

Kinoshita, Masashi; Nakajima, Riho; Shinohara, Harumichi; Miyashita, Katsuyoshi; Tanaka, Shingo; Okita, Hirokazu; Nakada, Mitsutoshi; Hayashi, Yutaka

2016-10-01

OBJECTIVE Although the right prefrontal region is regarded as a silent area, chronic deficits of the executive function, including working memory (WM), could occur after resection of a right prefrontal glioma. This may be overlooked by postoperative standard examinations, and the disabilities could affect the patient's professional life. The right prefrontal region is a part of the frontoparietal network and is subserved by the superior longitudinal fasciculus (SLF); however, the role of the SLF in spatial WM is unclear. This study investigated a persistent spatial WM deficit in patients who underwent right prefrontal glioma resection, and evaluated the relationship between the spatial WM deficit and the SLF. METHODS Spatial WM was examined in 24 patients who underwent prefrontal glioma resection (right, n = 14; left, n = 10) and in 14 healthy volunteers using a spatial 2-back task during the long-term postoperative period. The neural correlates of spatial WM were evaluated using lesion mapping and voxel-based lesion-symptom mapping. In addition, the spatial 2-back task was performed during surgery under direct subcortical electrical stimulation in 2 patients with right prefrontal gliomas. RESULTS Patients with a right prefrontal lesion had a significant chronic spatial WM deficit. Voxel-based lesion-symptom mapping analysis revealed a significant correlation between spatial WM deficit and the region that overlapped the first and second segments of the SLF (SLF I and SLF II). Two patients underwent awake surgery and had difficulties providing the correct responses in the spatial 2-back task with direct subcortical electrical stimulation on the SLF I, which was preserved and confirmed by postoperative diffusion tensor imaging tractography. These patients exhibited no spatial WM deficits during the postoperative immediate and long-term periods. CONCLUSIONS Spatial WM deficits may persist in patients who undergo resection of the tumor located in the right prefrontal brain parenchyma. Injury to the dorsal frontoparietal subcortical white matter pathway, i.e., the SLF I or SLF I and II, could play a causal role in this chronic deficit. A persistent spatial WM deficit, without motor and language deficits, could affect the professional life of the patient. In such cases, awake surgery would be useful to detect the spatial WM network with appropriate task during tumor exploration.

A case for motor network contributions to schizophrenia symptoms: Evidence from resting-state connectivity.

PubMed

Bernard, Jessica A; Goen, James R M; Maldonado, Ted

2017-09-01

Though schizophrenia (SCZ) is classically defined based on positive symptoms and the negative symptoms of the disease prove to be debilitating for many patients, motor deficits are often present as well. A growing literature highlights the importance of motor systems and networks in the disease, and it may be the case that dysfunction in motor networks relates to the pathophysiology and etiology of SCZ. To test this and build upon recent work in SCZ and in at-risk populations, we investigated cortical and cerebellar motor functional networks at rest in SCZ and controls using publically available data. We analyzed data from 82 patients and 88 controls. We found key group differences in resting-state connectivity patterns that highlight dysfunction in motor circuits and also implicate the thalamus. Furthermore, we demonstrated that in SCZ, these resting-state networks are related to both positive and negative symptom severity. Though the ventral prefrontal cortex and corticostriatal pathways more broadly have been implicated in negative symptom severity, here we extend these findings to include motor-striatal connections, as increased connectivity between the primary motor cortex and basal ganglia was associated with more severe negative symptoms. Together, these findings implicate motor networks in the symptomatology of psychosis, and we speculate that these networks may be contributing to the etiology of the disease. Overt motor deficits in SCZ may signal underlying network dysfunction that contributes to the overall disease state. Hum Brain Mapp 38:4535-4545, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Broca’s area network in language function: a pooling-data connectivity study

PubMed Central

Bernal, Byron; Ardila, Alfredo; Rosselli, Monica

2015-01-01

Background and Objective: Modern neuroimaging developments have demonstrated that cognitive functions correlate with brain networks rather than specific areas. The purpose of this paper was to analyze the connectivity of Broca’s area based on language tasks. Methods: A connectivity modeling study was performed by pooling data of Broca’s activation in language tasks. Fifty-seven papers that included 883 subjects in 84 experiments were analyzed. Analysis of Likelihood Estimates of pooled data was utilized to generate the map; thresholds at p < 0.01 were corrected for multiple comparisons and false discovery rate. Resulting images were co-registered into MNI standard space. Results: A network consisting of 16 clusters of activation was obtained. Main clusters were located in the frontal operculum, left posterior temporal region, supplementary motor area, and the parietal lobe. Less common clusters were seen in the sub-cortical structures including the left thalamus, left putamen, secondary visual areas, and the right cerebellum. Conclusion: Broca’s area-44-related networks involved in language processing were demonstrated utilizing a pooling-data connectivity study. Significance, interpretation, and limitations of the results are discussed. PMID:26074842

Brain network of semantic integration in sentence reading: insights from independent component analysis and graph theoretical analysis.

PubMed

Ye, Zheng; Doñamayor, Nuria; Münte, Thomas F

2014-02-01

A set of cortical and sub-cortical brain structures has been linked with sentence-level semantic processes. However, it remains unclear how these brain regions are organized to support the semantic integration of a word into sentential context. To look into this issue, we conducted a functional magnetic resonance imaging (fMRI) study that required participants to silently read sentences with semantically congruent or incongruent endings and analyzed the network properties of the brain with two approaches, independent component analysis (ICA) and graph theoretical analysis (GTA). The GTA suggested that the whole-brain network is topologically stable across conditions. The ICA revealed a network comprising the supplementary motor area (SMA), left inferior frontal gyrus, left middle temporal gyrus, left caudate nucleus, and left angular gyrus, which was modulated by the incongruity of sentence ending. Furthermore, the GTA specified that the connections between the left SMA and left caudate nucleus as well as that between the left caudate nucleus and right thalamus were stronger in response to incongruent vs. congruent endings. Copyright © 2012 Wiley Periodicals, Inc.

Concurrent white matter bundles and grey matter networks using independent component analysis.

PubMed

O'Muircheartaigh, Jonathan; Jbabdi, Saad

2018-04-15

Developments in non-invasive diffusion MRI tractography techniques have permitted the investigation of both the anatomy of white matter pathways connecting grey matter regions and their structural integrity. In parallel, there has been an expansion in automated techniques aimed at parcellating grey matter into distinct regions based on functional imaging. Here we apply independent component analysis to whole-brain tractography data to automatically extract brain networks based on their associated white matter pathways. This method decomposes the tractography data into components that consist of paired grey matter 'nodes' and white matter 'edges', and automatically separates major white matter bundles, including known cortico-cortical and cortico-subcortical tracts. We show how this framework can be used to investigate individual variations in brain networks (in terms of both nodes and edges) as well as their associations with individual differences in behaviour and anatomy. Finally, we investigate correspondences between tractography-based brain components and several canonical resting-state networks derived from functional MRI. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Detecting Mild Traumatic Brain Injury Using Resting State Magnetoencephalographic Connectivity

PubMed Central

da Costa, Leodante; Jetly, Rakesh; Pang, Elizabeth W.; Taylor, Margot J.

2016-01-01

Accurate means to detect mild traumatic brain injury (mTBI) using objective and quantitative measures remain elusive. Conventional imaging typically detects no abnormalities despite post-concussive symptoms. In the present study, we recorded resting state magnetoencephalograms (MEG) from adults with mTBI and controls. Atlas-guided reconstruction of resting state activity was performed for 90 cortical and subcortical regions, and calculation of inter-regional oscillatory phase synchrony at various frequencies was performed. We demonstrate that mTBI is associated with reduced network connectivity in the delta and gamma frequency range (>30 Hz), together with increased connectivity in the slower alpha band (8–12 Hz). A similar temporal pattern was associated with correlations between network connectivity and the length of time between the injury and the MEG scan. Using such resting state MEG network synchrony we were able to detect mTBI with 88% accuracy. Classification confidence was also correlated with clinical symptom severity scores. These results provide the first evidence that imaging of MEG network connectivity, in combination with machine learning, has the potential to accurately detect and determine the severity of mTBI. PMID:27906973

A computational framework for the detection of subcortical brain dysmaturation in neonatal MRI using 3D Convolutional Neural Networks.

PubMed

Ceschin, Rafael; Zahner, Alexandria; Reynolds, William; Gaesser, Jenna; Zuccoli, Giulio; Lo, Cecilia W; Gopalakrishnan, Vanathi; Panigrahy, Ashok

2018-05-21

Deep neural networks are increasingly being used in both supervised learning for classification tasks and unsupervised learning to derive complex patterns from the input data. However, the successful implementation of deep neural networks using neuroimaging datasets requires adequate sample size for training and well-defined signal intensity based structural differentiation. There is a lack of effective automated diagnostic tools for the reliable detection of brain dysmaturation in the neonatal period, related to small sample size and complex undifferentiated brain structures, despite both translational research and clinical importance. Volumetric information alone is insufficient for diagnosis. In this study, we developed a computational framework for the automated classification of brain dysmaturation from neonatal MRI, by combining a specific deep neural network implementation with neonatal structural brain segmentation as a method for both clinical pattern recognition and data-driven inference into the underlying structural morphology. We implemented three-dimensional convolution neural networks (3D-CNNs) to specifically classify dysplastic cerebelli, a subset of surface-based subcortical brain dysmaturation, in term infants born with congenital heart disease. We obtained a 0.985 ± 0. 0241-classification accuracy of subtle cerebellar dysplasia in CHD using 10-fold cross-validation. Furthermore, the hidden layer activations and class activation maps depicted regional vulnerability of the superior surface of the cerebellum, (composed of mostly the posterior lobe and the midline vermis), in regards to differentiating the dysplastic process from normal tissue. The posterior lobe and the midline vermis provide regional differentiation that is relevant to not only to the clinical diagnosis of cerebellar dysplasia, but also genetic mechanisms and neurodevelopmental outcome correlates. These findings not only contribute to the detection and classification of a subset of neonatal brain dysmaturation, but also provide insight to the pathogenesis of cerebellar dysplasia in CHD. In addition, this is one of the first examples of the application of deep learning to a neuroimaging dataset, in which the hidden layer activation revealed diagnostically and biologically relevant features about the clinical pathogenesis. The code developed for this project is open source, published under the BSD License, and designed to be generalizable to applications both within and beyond neonatal brain imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Altered Brain Network Segregation in Fragile X Syndrome Revealed by Structural Connectomics.

PubMed

Bruno, Jennifer Lynn; Hosseini, S M Hadi; Saggar, Manish; Quintin, Eve-Marie; Raman, Mira Michelle; Reiss, Allan L

2017-03-01

Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder, is associated with significant behavioral, social, and neurocognitive deficits. Understanding structural brain network topology in FXS provides an important link between neurobiological and behavioral/cognitive symptoms of this disorder. We investigated the connectome via whole-brain structural networks created from group-level morphological correlations. Participants included 100 individuals: 50 with FXS and 50 with typical development, age 11-23 years. Results indicated alterations in topological properties of structural brain networks in individuals with FXS. Significantly reduced small-world index indicates a shift in the balance between network segregation and integration and significantly reduced clustering coefficient suggests that reduced local segregation shifted this balance. Caudate and amygdala were less interactive in the FXS network further highlighting the importance of subcortical region alterations in the neurobiological signature of FXS. Modularity analysis indicates that FXS and typically developing groups' networks decompose into different sets of interconnected sub networks, potentially indicative of aberrant local interconnectivity in individuals with FXS. These findings advance our understanding of the effects of fragile X mental retardation protein on large-scale brain networks and could be used to develop a connectome-level biological signature for FXS. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Information processing in the primate visual system - An integrated systems perspective

NASA Technical Reports Server (NTRS)

Van Essen, David C.; Anderson, Charles H.; Felleman, Daniel J.

1992-01-01

The primate visual system contains dozens of distinct areas in the cerebral cortex and several major subcortical structures. These subdivisions are extensively interconnected in a distributed hierarchical network that contains several intertwined processing streams. A number of strategies are used for efficient information processing within this hierarchy. These include linear and nonlinear filtering, passage through information bottlenecks, and coordinated use of multiple types of information. In addition, dynamic regulation of information flow within and between visual areas may provide the computational flexibility needed for the visual system to perform a broad spectrum of tasks accurately and at high resolution.

Beta-thalassemia intermedia associated with moyamoya syndrome.

PubMed

Göksel, Basak Karakurum; Ozdogu, Hakan; Yildirim, Tulin; Oğuzkurt, Levent; Asma, Suheyl

2010-07-01

Moyamoya syndrome (MMS) is a progressive disorder. We report a 19-year-old boy with beta-thalassemia who presented with a left hemiparesis. Brain MRI showed old middle cerebral artery and left frontal subcortical white matter infarcts. Brain magnetic resonance angiography and digital subtraction angiography revealed occlusion of the bilateral internal carotid arteries with a rich network of basal collateral vessels. To our knowledge this is the third report of beta-thalassemia intermedia and MMS, and the first report of a patient in Turkey. It emphasizes the potential for cerebral infarct due to anemia, protein S and thrombocytosis.

Large-scale network integration in the human brain tracks temporal fluctuations in memory encoding performance.

PubMed

Keerativittayayut, Ruedeerat; Aoki, Ryuta; Sarabi, Mitra Taghizadeh; Jimura, Koji; Nakahara, Kiyoshi

2018-06-18

Although activation/deactivation of specific brain regions have been shown to be predictive of successful memory encoding, the relationship between time-varying large-scale brain networks and fluctuations of memory encoding performance remains unclear. Here we investigated time-varying functional connectivity patterns across the human brain in periods of 30-40 s, which have recently been implicated in various cognitive functions. During functional magnetic resonance imaging, participants performed a memory encoding task, and their performance was assessed with a subsequent surprise memory test. A graph analysis of functional connectivity patterns revealed that increased integration of the subcortical, default-mode, salience, and visual subnetworks with other subnetworks is a hallmark of successful memory encoding. Moreover, multivariate analysis using the graph metrics of integration reliably classified the brain network states into the period of high (vs. low) memory encoding performance. Our findings suggest that a diverse set of brain systems dynamically interact to support successful memory encoding. © 2018, Keerativittayayut et al.

The experience of art: insights from neuroimaging.

PubMed

Nadal, Marcos

2013-01-01

The experience of art is a complex one. It emerges from the interaction of multiple cognitive and affective processes. Neuropsychological and neuroimaging studies are revealing the broadly distributed network of brain regions upon which it relies. This network can be divided into three functional components: (i) prefrontal, parietal, and temporal cortical regions support evaluative judgment, attentional processing, and memory retrieval; (ii) the reward circuit, including cortical, subcortical regions, and some of its regulators, is involved in the generation of pleasurable feelings and emotions, and the valuation and anticipation of reward; and (iii) attentional modulation of activity in low-, mid-, and high-level cortical sensory regions enhances the perceptual processing of certain features, relations, locations, or objects. Understanding how these regions act in concert to produce unique and moving art experiences and determining the impact of personal and cultural meaning and context on this network the biological foundation of the experience of art--remain future challenges. © 2013 Elsevier B.V. All rights reserved.

The development of hub architecture in the human functional brain network.

PubMed

Hwang, Kai; Hallquist, Michael N; Luna, Beatriz

2013-10-01

Functional hubs are brain regions that play a crucial role in facilitating communication among parallel, distributed brain networks. The developmental emergence and stability of hubs, however, is not well understood. The current study used measures of network topology drawn from graph theory to investigate the development of functional hubs in 99 participants, 10-20 years of age. We found that hub architecture was evident in late childhood and was stable from adolescence to early adulthood. Connectivity between hub and non-hub ("spoke") regions, however, changed with development. From childhood to adolescence, the strength of connections between frontal hubs and cortical and subcortical spoke regions increased. From adolescence to adulthood, hub-spoke connections with frontal hubs were stable, whereas connectivity between cerebellar hubs and cortical spoke regions increased. Our findings suggest that a developmentally stable functional hub architecture provides the foundation of information flow in the brain, whereas connections between hubs and spokes continue to develop, possibly supporting mature cognitive function.

Neural networks involved in learning lexical-semantic and syntactic information in a second language.

PubMed

Mueller, Jutta L; Rueschemeyer, Shirley-Ann; Ono, Kentaro; Sugiura, Motoaki; Sadato, Norihiro; Nakamura, Akinori

2014-01-01

The present study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of language acquisition in a realistic learning environment. Japanese native speakers were trained in a miniature version of German prior to fMRI scanning. During scanning they listened to (1) familiar sentences, (2) sentences including a novel sentence structure, and (3) sentences containing a novel word while visual context provided referential information. Learning-related decreases of brain activation over time were found in a mainly left-hemispheric network comprising classical frontal and temporal language areas as well as parietal and subcortical regions and were largely overlapping for novel words and the novel sentence structure in initial stages of learning. Differences occurred at later stages of learning during which content-specific activation patterns in prefrontal, parietal and temporal cortices emerged. The results are taken as evidence for a domain-general network supporting the initial stages of language learning which dynamically adapts as learners become proficient.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) associated with a novel C82R mutation in the NOTCH3 gene.

PubMed

Zea-Sevilla, M Ascensión; Bermejo-Velasco, Pedro; Serrano-Heranz, Regino; Calero, Miguel

2015-01-01

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited cerebrovascular disease associated with mutations in the NOTCH3 gene on chromosome 19, and represents the most common hereditary stroke disorder. We describe a pedigree, which suffered the classical clinical CADASIL pattern of migraine headaches, recurrent subcortical infarcts, and subcortical dementia, associated with a previously undescribed missense mutation (c.[244T>C], p.[C82R]) in NOTCH3. This new mutation extends the list of known pathogenic mutations responsible for CADASIL, which are associated with an odd number of cysteine residues within any of the epidermal growth factor-like repeats of Notch3 receptor protein.

Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

PubMed

Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

2013-01-01

Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.

Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

PubMed Central

Bolitho, Samuel J.; Naismith, Sharon L.; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R.; Lewis, Simon J. G.

2013-01-01

Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms. PMID:24278399

Cognitive sequelae of methanol poisoning involve executive dysfunction and memory impairment in cross-sectional and long-term perspective.

PubMed

Bezdicek, O; Michalec, J; Vaneckova, M; Klempir, J; Liskova, I; Seidl, Z; Janikova, B; Miovsky, M; Hubacek, J; Diblik, P; Kuthan, P; Pilin, A; Kurcova, I; Fenclova, Z; Petrik, V; Navratil, T; Pelclova, D; Zakharov, S; Ruzicka, E

2017-03-01

Methanol poisoning leads to lesions in the basal ganglia and subcortical white matter, as well as to demyelination and atrophy of the optic nerve. However, information regarding cognitive deficits in a large methanol sample is lacking. The principal aim of the present study was to identify the cognitive sequelae of methanol poisoning and their morphological correlates. A sample of 50 patients (METH; age 48 ± 13 years), 3-8 months after methanol poisoning, and 57 control subjects (CS; age 49 ± 13 years) were administered a neuropsychological battery. Forty-six patients were followed in 2 years' perspective. Patients additionally underwent 1.5T magnetic resonance imaging (MRI). Three biochemical and toxicological metabolic markers and a questionnaire regarding alcohol abuse facilitated the classification of 24 patients with methanol poisoning without alcohol abuse (METHna) and 22 patients with methanol poisoning and alcohol abuse (METHa). All groups were compared to a control group of similar size, and matched for age, education, premorbid intelligence level, global cognitive performance, and level of depressive symptoms. Using hierarchical multiple regression we found significant differences between METH and CS, especially in executive and memory domains. METHa showed a similar pattern of cognitive impairment with generally more severe executive dysfunction. Moreover, all METH patients with extensive involvement on brain MRI (lesions in ≥2 anatomical regions) had a more severe cognitive impairment. From a longitudinal perspective, we did not find any changes in their cognitive functioning after 2 years' follow-up. Our findings suggest that methanol poisoning is associated with executive dysfunction and explicit memory impairment, supposedly due to basal ganglia dysfunction and disruption of frontostriatal circuitry proportional to the number of brain lesions, and that these changes are persistent after 2 years' follow-up. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolic networks in epilepsy by MR spectroscopic imaging.

PubMed

Pan, J W; Spencer, D D; Kuzniecky, R; Duckrow, R B; Hetherington, H; Spencer, S S

2012-12-01

The concept of an epileptic network has long been suggested from both animal and human studies of epilepsy. Based on the common observation that the MR spectroscopic imaging measure of NAA/Cr is sensitive to neuronal function and injury, we use this parameter to assess for the presence of a metabolic network in mesial temporal lobe epilepsy (MTLE) patients. A multivariate factor analysis is performed with controls and MTLE patients, using NAA/Cr measures from 12 loci: the bilateral hippocampi, thalami, basal ganglia, and insula. The factor analysis determines which and to what extent these loci are metabolically covarying. We extract two independent factors that explain the data's variability in control and MTLE patients. In controls, these factors characterize a 'thalamic' and 'dominant subcortical' function. The MTLE patients also exhibit a 'thalamic' factor, in addition to a second factor involving the ipsilateral insula and bilateral basal ganglia. These data suggest that MTLE patients demonstrate a metabolic network that involves the thalami, also seen in controls. The MTLE patients also display a second set of metabolically covarying regions that may be a manifestation of the epileptic network that characterizes limbic seizure propagation. © 2012 John Wiley & Sons A/S.

Kinematics of gray crescent formation in Xenopus eggs: the displacement of subcortical cytoplasm relative to the egg surface.

PubMed

Vincent, J P; Oster, G F; Gerhart, J C

1986-02-01

Specification of the amphibian dorso-ventral axis takes place in the period between fertilization and first cleavage when the gray crescent forms. In the course of gray crescent formation, the egg reorganizes its periphery by a movement for which two descriptions have been given. According to the "rotation hypothesis," which was originated and supported for Rana eggs, the entire egg cortex rotates by an arc of 30 degrees relative to the stationary subcortical cytoplasm, leaving the crescent as a zone of altered coloration. The "contraction hypothesis" on the other hand, which was proposed for Xenopus and Rana eggs, asserts that there is a cortical contraction focused at the sperm entry point that leads to stretching of the opposite equatorial zone at which the crescent appears. We have reinvestigated the case of Xenopus eggs by imprinting one kind of fluorescent dye pattern (Nile blue) onto the subcortical cytoplasm and another kind (fluorescein-lectin) onto the egg surface. When the egg surface is held fixed by embedding the egg in gelatin, two major movements of the subcortical cytoplasm are observable. First, starting at time 0.3 (30% of the time between fertilization and first cleavage), the animal hemisphere subcortical cytoplasm converges toward a point, while the vegetal hemisphere is quiescent. This convergence continues with decreasing strength until approximately 0.8 of the first cell cycle. Second, at 0.45, an overall rotation of the animal and vegetal subcortical cytoplasm commences, superimposed on the animal hemisphere convergence. By 0.8-0.9 the rotation is complete, having accomplished a 30 degrees displacement of the subcortical cytoplasm relative to the surface. This rotation reliably locates the future dorsal midline of the embryo at the meridian on which the displacement of the subcortical cytoplasm is greatest in a vegetal direction. In normal unembedded eggs, when the egg surface is free to move, it rotates 30 degrees relative to the subcortical cytoplasm, which remains stationary in a position of gravitational equilibrium. Although both a convergence and rotation occur in the Xenopus egg, we give evidence that the rotation, not the convergence (perhaps equated with contraction), specifies the embryo's prospective axis. Even though the Xenopus egg does not form a classical gray crescent, due to its particular pigment distribution, the reorganization process which specifies the future embryonic axis resembles that of the Rana egg.

An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans.

PubMed

Reardon, Paul Kirkpatrick; Clasen, Liv; Giedd, Jay N; Blumenthal, Jonathan; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin

2016-02-24

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. Copyright © 2016 the authors 0270-6474/16/362438-11$15.00/0.

Cortical and subcortical mapping of language areas: correlation of functional MRI and tractography in a 3T scanner with intraoperative cortical and subcortical stimulation in patients with brain tumors located in eloquent areas.

PubMed

Jiménez de la Peña, M; Gil Robles, S; Recio Rodríguez, M; Ruiz Ocaña, C; Martínez de Vega, V

2013-01-01

To describe the detection of cortical areas and subcortical pathways involved in language observed in MRI activation studies and tractography in a 3T MRI scanner and to correlate the findings of these functional studies with direct intraoperative cortical and subcortical stimulation. We present a series of 14 patients with focal brain tumors adjacent to eloquent brain areas. All patients underwent neuropsychological evaluation before and after surgery. All patients underwent MRI examination including structural sequences, perfusion imaging, spectroscopy, functional imaging to determine activation of motor and language areas, and 3D tractography. All patients underwent cortical mapping through cortical and subcortical stimulation during the operation to resect the tumor. Postoperative follow-up studies were done 24 hours after surgery. The correlation of motor function and of the corticospinal tract determined by functional MRI and tractography with intraoperative mapping of cortical and subcortical motor areas was complete. The eloquent brain areas of language expression and reception were strongly correlated with intraoperative cortical mapping in all but two cases (a high grade infiltrating glioma and a low grade glioma located in the frontal lobe). 3D tractography identified the arcuate fasciculus, the lateral part of the superior longitudinal fasciculus, the subcallosal fasciculus, the inferior fronto-occipital fasciculus, and the optic radiations, which made it possible to mark the limits of the resection. The correlation with the subcortical mapping of the anatomic arrangement of the fasciculi with respect to the lesions was complete. The best treatment for brain tumors is maximum resection without associated deficits, so high quality functional studies are necessary for preoperative planning. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

Physical fitness and shapes of subcortical brain structures in children.

PubMed

Ortega, Francisco B; Campos, Daniel; Cadenas-Sanchez, Cristina; Altmäe, Signe; Martínez-Zaldívar, Cristina; Martín-Matillas, Miguel; Catena, Andrés; Campoy, Cristina

2017-03-27

A few studies have recently reported that higher cardiorespiratory fitness is associated with higher volumes of subcortical brain structures in children. It is, however, unknown how different fitness measures relate to shapes of subcortical brain nuclei. We aimed to examine the association of the main health-related physical fitness components with shapes of subcortical brain structures in a sample of forty-four Spanish children aged 9·7 (sd 0·2) years from the NUtraceuticals for a HEALthier life project. Cardiorespiratory fitness, muscular strength and speed agility were assessed using valid and reliable tests (ALPHA-fitness test battery). Shape of the subcortical brain structures was assessed by MRI, and its relationship with fitness was examined after controlling for a set of potential confounders using a partial correlation permutation approach. Our results showed that all physical fitness components studied were significantly related to the shapes of subcortical brain nuclei. These associations were both positive and negative, indicating that a higher level of fitness in childhood is related to both expansions and contractions in certain regions of the accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. Cardiorespiratory fitness was mainly associated with expansions, whereas handgrip was mostly associated with contractions in the structures studied. Future randomised-controlled trials will confirm or contrast our findings, demonstrating whether changes in fitness modify the shapes of brain structures and the extent to which those changes influence cognitive function.

Probing Intrinsic Resting-State Networks in the Infant Rat Brain

PubMed Central

Bajic, Dusica; Craig, Michael M.; Borsook, David; Becerra, Lino

2016-01-01

Resting-state functional magnetic resonance imaging (rs-fMRI) measures spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal in the absence of external stimuli. It has become a powerful tool for mapping large-scale brain networks in humans and animal models. Several rs-fMRI studies have been conducted in anesthetized and awake adult rats, reporting consistent patterns of brain activity at the systems level. However, the evolution to adult patterns of resting-state activity has not yet been evaluated and quantified in the developing rat brain. In this study, we hypothesized that large-scale intrinsic networks would be easily detectable but not fully established as specific patterns of activity in lightly anesthetized 2-week-old rats (N = 11). Independent component analysis (ICA) identified 8 networks in 2-week-old-rats. These included Default mode, Sensory (Exteroceptive), Salience (Interoceptive), Basal Ganglia-Thalamic-Hippocampal, Basal Ganglia, Autonomic, Cerebellar, as well as Thalamic-Brainstem networks. Many of these networks consisted of more than one component, possibly indicative of immature, underdeveloped networks at this early time point. Except for the Autonomic network, infant rat networks showed reduced connectivity with subcortical structures in comparison to previously published adult networks. Reported slow fluctuations in the BOLD signal that correspond to functionally relevant resting-state networks in 2-week-old rats can serve as an important tool for future studies of brain development in the settings of different pharmacological applications or disease. PMID:27803653

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

PubMed

Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

2015-06-01

The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

Photosensitive epilepsy is associated with reduced inhibition of alpha rhythm generating networks

PubMed Central

Vaudano, Anna Elisabetta; Ruggieri, Andrea; Avanzini, Pietro; Gessaroli, Giuliana; Cantalupo, Gaetano; Coppola, Antonietta; Sisodiya, Sanjay M.

2017-01-01

Abstract See Hamandi (doi:10.1093/awx049) for a scientific commentary on this article. Photosensitivity is a condition in which lights induce epileptiform activities. This abnormal electroencephalographic response has been associated with hyperexcitability of the visuo-motor system. Here, we evaluate if intrinsic dysfunction of this network is present in brain activity at rest, independently of any stimulus and of any paroxysmal electroencephalographic activity. To address this issue, we investigated the haemodynamic correlates of the spontaneous alpha rhythm, which is considered the hallmark of the brain resting state, in photosensitive patients and in people without photosensitivity. Second, we evaluated the whole-brain functional connectivity of the visual thalamic nuclei in the various populations of subjects under investigation. Forty-four patients with epilepsy and 16 healthy control subjects underwent an electroencephalography-correlated functional magnetic resonance imaging study, during an eyes-closed condition. The following patient groups were included: (i) genetic generalized epilepsy with photosensitivity, 16 subjects (mean age 25 ± 10 years); (ii) genetic generalized epilepsy without photosensitivity, 13 patients (mean age 25 ± 11 years); (iii) focal epilepsy, 15 patients (mean age 25 ± 9 years). For each subject, the posterior alpha power variations were convolved with the standard haemodynamic response function and used as a regressor. Within- and between-groups second level analyses were performed. Whole brain functional connectivity was evaluated for two thalamic regions of interest, based on the haemodynamic findings, which included the posterior thalamus (pulvinar) and the medio-dorsal thalamic nuclei. Genetic generalized epilepsy with photosensitivity demonstrated significantly greater mean alpha-power with respect to controls and other epilepsy groups. In photosensitive epilepsy, alpha-related blood oxygen level-dependent signal changes demonstrated lower decreases relative to all other groups in the occipital, sensory-motor, anterior cingulate and supplementary motor cortices. Coherently, the same brain regions demonstrated abnormal connectivity with the visual thalamus only in epilepsy patients with photosensitivity. As predicted, our findings indicate that the cortical-subcortical network generating the alpha oscillation at rest is different in people with epilepsy and visual sensitivity. This difference consists of a decreased alpha-related inhibition of the visual cortex and sensory-motor networks at rest. These findings represent the substrate of the clinical manifestations (i.e. myoclonus) of the photoparoxysmal response. Moreover, our results provide the first evidence of the existence of a functional link between the circuits that trigger the visual sensitivity phenomenon and those that generate the posterior alpha rhythm. PMID:28334965

The Human Thalamus Is an Integrative Hub for Functional Brain Networks

PubMed Central

Bertolero, Maxwell A.

2017-01-01

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks. PMID:28450543

Aging and functional brain networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomasi D.; Tomasi, D.; Volkow, N.D.

2011-07-11

Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associatedmore » with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.« less

Cingulate, Frontal and Parietal Cortical Dysfunction in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Bush, George

2011-01-01

Functional and structural neuroimaging have identified abnormalities of the brain that are likely to contribute to the neuropathophysiology of attention-deficit/hyperactivity disorder (ADHD). In particular, hypofunction of the brain regions comprising the cingulo-frontal-parietal (CFP) cognitive-attention network have been consistently observed across studies. These are major components of neural systems that are relevant to ADHD, including cognitive/attention networks, motor systems and reward/feedback-based processing systems. Moreover, these areas interact with other brain circuits that have been implicated in ADHD, such as the “default mode” resting state network. ADHD imaging data related to CFP network dysfunction will be selectively highlighted here to help facilitate its integration with the other information presented in this special issue. Together, these reviews will help shed light on the neurobiology of ADHD. PMID:21489409

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder.

PubMed

Baune, Bernhard T; Brignone, Mélanie; Larsen, Klaus Groes

2018-02-01

Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

PubMed Central

Liu, Yaou; Duan, Yunyun; Li, Kuncheng

2015-01-01

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID:26539535

Neurofeedback of visual food cue reactivity: a potential avenue to alter incentive sensitization and craving.

PubMed

Ihssen, Niklas; Sokunbi, Moses O; Lawrence, Andrew D; Lawrence, Natalia S; Linden, David E J

2017-06-01

FMRI-based neurofeedback transforms functional brain activation in real-time into sensory stimuli that participants can use to self-regulate brain responses, which can aid the modification of mental states and behavior. Emerging evidence supports the clinical utility of neurofeedback-guided up-regulation of hypoactive networks. In contrast, down-regulation of hyperactive neural circuits appears more difficult to achieve. There are conditions though, in which down-regulation would be clinically useful, including dysfunctional motivational states elicited by salient reward cues, such as food or drug craving. In this proof-of-concept study, 10 healthy females (mean age = 21.40 years, mean BMI = 23.53) who had fasted for 4 h underwent a novel 'motivational neurofeedback' training in which they learned to down-regulate brain activation during exposure to appetitive food pictures. FMRI feedback was given from individually determined target areas and through decreases/increases in food picture size, thus providing salient motivational consequences in terms of cue approach/avoidance. Our preliminary findings suggest that motivational neurofeedback is associated with functionally specific activation decreases in diverse cortical/subcortical regions, including key motivational areas. There was also preliminary evidence for a reduction of hunger after neurofeedback and an association between down-regulation success and the degree of hunger reduction. Decreasing neural cue responses by motivational neurofeedback may provide a useful extension of existing behavioral methods that aim to modulate cue reactivity. Our pilot findings indicate that reduction of neural cue reactivity is not achieved by top-down regulation but arises in a bottom-up manner, possibly through implicit operant shaping of target area activity.

Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats.

PubMed

Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Tingting

2015-01-15

The involvement of dopamine (DA) neuron loss in the etiology of Parkinson's disease has been well documented. The neural mechanisms underlying the effects of DA loss and the resultant motor dysfunction remain unknown. To gain insights into how loss of DA disrupts the electrical processes in the cortico-subcortical network, the present study explores the effects of DA neuron depletion on electrical activity in the primary motor cortex (M1), on the external and the internal segment of the globus pallidus (GPe and GPi respectively), and on their temporal relationships. Comparison of local field potentials (LFPs) in these brain regions from unilateral hemispheric DA neuron depleted rats and neurologically intact rats revealed that the spectrum power of LFPs in 12-70Hz (for M1, and GPe) and in 25-40Hz (for GPi) was significantly greater in the DA depleted rats than that in the control group. These changes were associated with a shortening of latency in LFP activities between M1 and GPe, from several hundred milliseconds in the intact animals to close to zero in the DA depleted animals. LFP oscillations in M1 were significantly more synchronized with those in GPe in the DA depleted rats compared with those in the control rats. By contrast, the synchronization of oscillation in LFP activities between M1 and GPi did not differ between the DA depleted and intact rats. Not surprisingly, rats that had DA neuron depletion spent more time along the ladder compared with the control rats. These data suggest that enhanced oscillatory activity and increased synchronization of LFPs may contribute to movement impairment in the rat model of Parkinson's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Mental States in Moving Shapes: Distinct Cortical and Subcortical Contributions to Theory of Mind Impairments in Dementia.

PubMed

Synn, Artemis; Mothakunnel, Annu; Kumfor, Fiona; Chen, Yu; Piguet, Olivier; Hodges, John R; Irish, Muireann

2018-01-01

Impaired capacity for Theory of Mind (ToM) represents one of the hallmark features of the behavioral variant of frontotemporal dementia (bvFTD) and is suggested to underpin an array of socioemotional disturbances characteristic of this disorder. In contrast, while social processing typically remains intact in Alzheimer's disease (AD), the cognitive loading of socioemotional tasks may adversely impact mentalizing performance in AD. Here, we employed the Frith-Happé animations as a dynamic on-line assessment of mentalizing capacity with reduced incidental task demands in 18 bvFTD, 18 AD, and 25 age-matched Controls. Participants viewed silent animations in which geometric shapes interact in Random, Goal-Directed, and ToM conditions. An exclusive deficit in ToM classification was observed in bvFTD relative to Controls, while AD patients were impaired in the accurate classification of both Random and ToM trials. Correlation analyses revealed robust associations between ToM deficits and carer ratings of affective empathy disruption in bvFTD, and with episodic memory dysfunction in AD. Voxel-based morphometry analyses further identified dissociable neural correlates contingent on patient group. A distributed network of medial prefrontal, frontoinsular, striatal, lateral temporal, and parietal regions were implicated in the bvFTD group, whereas the right hippocampus correlated with task performance in AD. Notably, subregions of the cerebellum, including lobules I-IV and V, bilaterally were implicated in task performance irrespective of patient group. Our findings reveal new insights into the mechanisms potentially mediating ToM disruption in dementia syndromes, and suggest that the cerebellum may play a more prominent role in social cognition than previously appreciated.

Impaired orienting in youth with Internet Addiction: Evidence from the Attention Network Task (ANT).

PubMed

Fu, Jia; Xu, Peng; Zhao, Lun; Yu, Guoming

2018-06-01

An important theory of attention suggests that there are three separate networks that execute discrete cognitive functions: alerting, orienting and conflict networks. Recent studies showed that there was a dysfunction of attention in Internet Addiction. In order to investigate the underlying mechanism of attention dysfunction in Internet Addiction, we recorded performance related to the Attentional Network Test (ANT) in youth. The ANT, a behavioral assay of the functional integrity of attention networks, was used to examine the performance in Internet Addiction and healthy controls. Performance on the ANT clearly differentiated the participants with and without Internet Addiction in terms of mean reaction times (RTs). Compared with control group, the Internet Addiction group detected targets more slowly and this effect was evident only for spatial cue condition. The Internet Addiction group demonstrated deficits in the orienting network in terms of slower RT. There was no demonstration of a deficit in both the alerting and conflict network in Internet Addiction on this task. The youth with Internet Addiction demonstrated deficits in the orienting network but normal functioning of the alerting and conflict attention networks. Copyright © 2017 Elsevier B.V. All rights reserved.

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

PubMed

Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Narkhede, Atul; Griffith, Erica Y; Cohen, Ronald; Sweet, Lawrence H; Josephson, Richard; Hughes, Joel; Gunstad, John

2016-01-01

Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

Clinical and Electrographic Correlates of Bilateral Independent Periodic Discharges.

PubMed

Freund, Brin; Gugger, James J; Reynolds, Alexandra; Tatum, William O; Claassen, Jan; Kaplan, Peter W

2018-05-01

Periodic discharges (PDs) are EEG patterns denoting brain dysfunction and ictal tendency. Their exact meaning regarding etiology and outcomes is not well known. In particular, bilateral independent PDs (BIPDs) are poorly described. We performed a retrospective, multicenter study evaluating neuroimaging, epileptic, clinical, and EEG correlates of BIPDs. Twenty-five patients studied with a mean Glasgow Coma Scale 6.5 and modified Rankin scale 3.9 who underwent EEG monitoring, mean duration 287 hours (range 0.75-3,216). Most common causes of BIPDs were cardiac arrest, Central Nervous System infections, and acute/chronic ischemic/hemorrhagic stroke. Most had subcortical and cortical injuries on neuroimaging. Most of the PDs ranged from 0.5 to 2 Hz in frequency, were of multiple phase types, and localized to the frontal head regions. Eighteen of 25 patients had clinical or electrographic seizures. There was a trend toward seizures in those with BIPDs with a history of epilepsy (P = 0.08) and acute metabolic dysfunction (P = 0.08), particularly with coincident acute structural lesions (P = 0.05). Seizures were predicted by bilaterally symmetric frequencies (P = 0.02) and trended toward higher likelihood with PD frequency <2 Hz (P = 0.08). Two of 25 patients survived past discharge with modified Rankin scale <3. Cardiac arrest was associated with withdrawal of life-sustaining therapy (P < 0.001). BIPDs arise from acute and chronic neurologic injuries, often associated with metabolic dysfunction. Outcomes are poor in this population. Seizures are common, particularly in patients with PDs that are of a lower frequency or are symmetric in frequency. Further study is warranted to evaluate the association between BIPDs and seizures, as well as functional and longer term outcomes.

Hubs of Anticorrelation in High-Resolution Resting-State Functional Connectivity Network Architecture.

PubMed

Gopinath, Kaundinya; Krishnamurthy, Venkatagiri; Cabanban, Romeo; Crosson, Bruce A

2015-06-01

A major focus of brain research recently has been to map the resting-state functional connectivity (rsFC) network architecture of the normal brain and pathology through functional magnetic resonance imaging. However, the phenomenon of anticorrelations in resting-state signals between different brain regions has not been adequately examined. The preponderance of studies on resting-state fMRI (rsFMRI) have either ignored anticorrelations in rsFC networks or adopted methods in data analysis, which have rendered anticorrelations in rsFC networks uninterpretable. The few studies that have examined anticorrelations in rsFC networks using conventional methods have found anticorrelations to be weak in strength and not very reproducible across subjects. Anticorrelations in rsFC network architecture could reflect mechanisms that subserve a number of important brain processes. In this preliminary study, we examined the properties of anticorrelated rsFC networks by systematically focusing on negative cross-correlation coefficients (CCs) among rsFMRI voxel time series across the brain with graph theory-based network analysis. A number of methods were implemented to enhance the neuronal specificity of resting-state functional connections that yield negative CCs, although at the cost of decreased sensitivity. Hubs of anticorrelation were seen in a number of cortical and subcortical brain regions. Examination of the anticorrelation maps of these hubs indicated that negative CCs in rsFC network architecture highlight a number of regulatory interactions between brain networks and regions, including reciprocal modulations, suppression, inhibition, and neurofeedback.

Advocacy for Kids: A View from the Residential Trenches.

ERIC Educational Resources Information Center

Parsons, Jon R.

1995-01-01

Presents the concept of advocacy in the trenches, wherein residential care staff intercede with and for dysfunctional families, dysfunctional children, and the bureaucracy. This advocacy emphasizes individualized treatment and case-by-case networking, focusing not on broad causes but on what is in the best interest of each child. (ET)

Neural correlates of childhood trauma with executive function in young healthy adults.

PubMed

Lu, Shaojia; Pan, Fen; Gao, Weijia; Wei, Zhaoguo; Wang, Dandan; Hu, Shaohua; Huang, Manli; Xu, Yi; Li, Lingjiang

2017-10-03

The aim of this study was to investigate the relationship among childhood trauma, executive impairments, and altered resting-state brain function in young healthy adults. Twenty four subjects with childhood trauma and 24 age- and gender-matched subjects without childhood trauma were recruited. Executive function was assessed by a series of validated test procedures. Localized brain activity was evaluated by fractional amplitude of low frequency fluctuation (fALFF) method and compared between two groups. Areas with altered fALFF were further selected as seeds in subsequent functional connectivity analysis. Correlations of fALFF and connectivity values with severity of childhood trauma and executive dysfunction were analyzed as well. Subjects with childhood trauma exhibited impaired executive function as assessed by Wisconsin Card Sorting Test and Stroop Color Word Test. Traumatic individuals also showed increased fALFF in the right precuneus and decreased fALFF in the right superior temporal gyrus. Significant correlations of specific childhood trauma severity with executive dysfunction and fALFF value in the right precuneus were found in the whole sample. In addition, individuals with childhood trauma also exhibited diminished precuneus-based connectivity in default mode network with left ventromedial prefrontal cortex, left orbitofrontal cortex, and right cerebellum. Decreased default mode network connectivity was also associated with childhood trauma severity and executive dysfunction. The present findings suggest that childhood trauma is associated with executive deficits and aberrant default mode network functions even in healthy adults. Moreover, this study demonstrates that executive dysfunction is related to disrupted default mode network connectivity.

Dysmorphic Facial Features and Other Clinical Characteristics in Two Patients with PEX1 Gene Mutations

PubMed Central

Gunduz, Mehmet

2016-01-01

Peroxisomal disorders are a group of genetically heterogeneous metabolic diseases related to dysfunction of peroxisomes. Dysmorphic features, neurological abnormalities, and hepatic dysfunction can be presenting signs of peroxisomal disorders. Here we presented dysmorphic facial features and other clinical characteristics in two patients with PEX1 gene mutation. Follow-up periods were 3.5 years and 1 year in the patients. Case I was one-year-old girl that presented with neurodevelopmental delay, hepatomegaly, bilateral hearing loss, and visual problems. Ophthalmologic examination suggested septooptic dysplasia. Cranial magnetic resonance imaging (MRI) showed nonspecific gliosis at subcortical and periventricular deep white matter. Case II was 2.5-year-old girl referred for investigation of global developmental delay and elevated liver enzymes. Ophthalmologic examination findings were consistent with bilateral nystagmus and retinitis pigmentosa. Cranial MRI was normal. Dysmorphic facial features including broad nasal root, low set ears, downward slanting eyes, downward slanting eyebrows, and epichantal folds were common findings in two patients. Molecular genetic analysis indicated homozygous novel IVS1-2A>G mutation in Case I and homozygous p.G843D (c.2528G>A) mutation in Case II in the PEX1 gene. Clinical findings and developmental prognosis vary in PEX1 gene mutation. Kabuki-like phenotype associated with liver pathology may indicate Zellweger spectrum disorders (ZSD). PMID:27882258

Subcortical laminar heterotopia and lissencephaly in two families: a single X linked dominant gene.

PubMed Central

Pinard, J M; Motte, J; Chiron, C; Brian, R; Andermann, E; Dulac, O

1994-01-01

Neuronal migration disorders can now be recognised by MRI. This paper reports two families in which the mothers had subcortical laminar heterotopia and four of their children had either similar heterotopia (two girls) or severe pachygyria or lissencephaly (two boys). Laminar heterotopia was more evident on MRI T2 weighted images. The patients had mild to severe epilepsy and mental retardation depending on the extent of cortical abnormalities. In these families, subcortical laminar heterotopia, pachygyria, and lissencephaly seem to share the same X linked or autosomal dominant gene. No chromosomal abnormalities, especially of chromosome 17, could be identified. For appropriate genetic counselling of the family of a child with lissencephaly or subcortical laminar heterotopia, MRI should be performed in parents or siblings with mental retardation or epilepsy. Images PMID:8057113

Paroxysmal dyskinesia as an unusual and only presentation of subcortical white matter ischaemia: a report of two cases.

PubMed

Norlinah, M I; Shahizon, A M M

2008-12-01

Secondary paroxysmal dyskinesias (PxD) have been previously reported in patients with multiple sclerosis, lacunar infarcts, head trauma, metabolic disorders such as hyperglycaemia, hypocalcaemia, migraine and central nervous system (CNS) infections. The causative lesions typically involve the basal ganglia structures, medulla and rarely the spinal cord. We report two patients who presented with paroxysmal dyskinesias as the only manifestation of subcortical white-matter ischaemia. Patient 1 presented with 3-year history of paroxysmal kinesigenic dyskinesia (PKD) and patient 2 with 6-month history of paroxysmal nonkinesigenic dyskinesia (PNKD). All investigations, including CSF oligoclonal bands were negative, except for a brain MRI which showed multiple, non-enhancing subcortical white matter lacunar infarcts. Therefore, subcortical white matter ischaemia should also be included in the differential diagnosis of PxD.

Comparison between Alzheimer's disease and subcortical vascular dementia: attentional cortex study in functional magnetic resonance imaging.

PubMed

Li, C; Zheng, J; Wang, J; Gui, L

2011-01-01

Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and the Stroop test were used to assess attentional cortex activation in patients with Alzheimer's disease, subcortical vascular dementia, and normal control subjects. Patients with Alzheimer's disease and subcortical vascular dementia demonstrated similar locations of cortical activation, including the bilateral middle and inferior frontal gyri, anterior cingulate and inferior parietal lobule in response to Stroop colour word stimuli. This activation was distinctly decreased in patients with dementia compared with normal control subjects. Different regions of the brain were activated in patients with Alzheimer's disease and subcortical vascular dementia compared with normal controls. fMRI is a useful tool for the study of dementia in humans and has some potential diagnostic value. Further studies with larger numbers of participants are required.

Cellular complexity in subcortical white matter: a distributed control circuit?

PubMed

Colombo, Jorge A

2018-03-01

The subcortical white matter (SWM) has been traditionally considered as a site for passive-neutral-information transfer through cerebral cortex association and projection fibers. Yet, the presence of subcortical neuronal and glial "interstitial" cells expressing immunolabelled neurotransmitters/neuromodulators and synaptic vesicular proteins, and recent immunohistochemical and electrophysiological observations on the rat visual cortex as well as interactive regulation of myelinating processes support the possibility that SWM nests subcortical, regionally variable, distributed neuronal-glial circuits, that could influence information transfer. Their hypothetical involvement in regulating the timing and signal transfer probability at the SWM axonal components ought to be considered and experimentally analysed. Thus, the "interstitial" neuronal cells-associated with local glial cells-traditionally considered to be vestigial and functionally inert under normal conditions, they may well turn to be critical in regulating information transfer at the SWM.

Reliability and statistical power analysis of cortical and subcortical FreeSurfer metrics in a large sample of healthy elderly.

PubMed

Liem, Franziskus; Mérillat, Susan; Bezzola, Ladina; Hirsiger, Sarah; Philipp, Michel; Madhyastha, Tara; Jäncke, Lutz

2015-03-01

FreeSurfer is a tool to quantify cortical and subcortical brain anatomy automatically and noninvasively. Previous studies have reported reliability and statistical power analyses in relatively small samples or only selected one aspect of brain anatomy. Here, we investigated reliability and statistical power of cortical thickness, surface area, volume, and the volume of subcortical structures in a large sample (N=189) of healthy elderly subjects (64+ years). Reliability (intraclass correlation coefficient) of cortical and subcortical parameters is generally high (cortical: ICCs>0.87, subcortical: ICCs>0.95). Surface-based smoothing increases reliability of cortical thickness maps, while it decreases reliability of cortical surface area and volume. Nevertheless, statistical power of all measures benefits from smoothing. When aiming to detect a 10% difference between groups, the number of subjects required to test effects with sufficient power over the entire cortex varies between cortical measures (cortical thickness: N=39, surface area: N=21, volume: N=81; 10mm smoothing, power=0.8, α=0.05). For subcortical regions this number is between 16 and 76 subjects, depending on the region. We also demonstrate the advantage of within-subject designs over between-subject designs. Furthermore, we publicly provide a tool that allows researchers to perform a priori power analysis and sensitivity analysis to help evaluate previously published studies and to design future studies with sufficient statistical power. Copyright © 2014 Elsevier Inc. All rights reserved.

Cortical and subcortical gray matter bases of cognitive deficits in REM sleep behavior disorder.

PubMed

Rahayel, Shady; Postuma, Ronald B; Montplaisir, Jacques; Génier Marchand, Daphné; Escudier, Frédérique; Gaubert, Malo; Bourgouin, Pierre-Alexandre; Carrier, Julie; Monchi, Oury; Joubert, Sven; Blanc, Frédéric; Gagnon, Jean-François

2018-05-15

To investigate cortical and subcortical gray matter abnormalities underlying cognitive impairment in patients with REM sleep behavior disorder (RBD) with or without mild cognitive impairment (MCI). Fifty-two patients with RBD, including 17 patients with MCI, were recruited and compared to 41 controls. All participants underwent extensive clinical assessments, neuropsychological examination, and 3-tesla MRI acquisition of T1 anatomical images. Vertex-based cortical analyses of volume, thickness, and surface area were performed to investigate cortical abnormalities between groups, whereas vertex-based shape analysis was performed to investigate subcortical structure surfaces. Correlations were performed to investigate associations between cortical and subcortical metrics, cognitive domains, and other markers of neurodegeneration (color discrimination, olfaction, and autonomic measures). Patients with MCI had cortical thinning in the frontal, cingulate, temporal, and occipital cortices, and abnormal surface contraction in the lenticular nucleus and thalamus. Patients without MCI had cortical thinning restricted to the frontal cortex. Lower patient performance in cognitive domains was associated with cortical and subcortical abnormalities. Moreover, impaired performance on olfaction, color discrimination, and autonomic measures was associated with thinning in the occipital lobe. Cortical and subcortical gray matter abnormalities are associated with cognitive status in patients with RBD, with more extensive patterns in patients with MCI. Our results highlight the importance of distinguishing between subgroups of patients with RBD according to cognitive status in order to better understand the neurodegenerative process in this population. © 2018 American Academy of Neurology.

Fast Detector/First Responder: Interactions between the Superior Colliculus-Pulvinar Pathway and Stimuli Relevant to Primates

PubMed Central

Soares, Sandra C.; Maior, Rafael S.; Isbell, Lynne A.; Tomaz, Carlos; Nishijo, Hisao

2017-01-01

Primates are distinguished from other mammals by their heavy reliance on the visual sense, which occurred as a result of natural selection continually favoring those individuals whose visual systems were more responsive to challenges in the natural world. Here we describe two independent but also interrelated visual systems, one cortical and the other subcortical, both of which have been modified and expanded in primates for different functions. Available evidence suggests that while the cortical visual system mainly functions to give primates the ability to assess and adjust to fluid social and ecological environments, the subcortical visual system appears to function as a rapid detector and first responder when time is of the essence, i.e., when survival requires very quick action. We focus here on the subcortical visual system with a review of behavioral and neurophysiological evidence that demonstrates its sensitivity to particular, often emotionally charged, ecological and social stimuli, i.e., snakes and fearful and aggressive facial expressions in conspecifics. We also review the literature on subcortical involvement during another, less emotional, situation that requires rapid detection and response—visually guided reaching and grasping during locomotion—to further emphasize our argument that the subcortical visual system evolved as a rapid detector/first responder, a function that remains in place today. Finally, we argue that investigating deficits in this subcortical system may provide greater understanding of Parkinson's disease and Autism Spectrum disorders (ASD). PMID:28261046

Dopamine replacement therapy and deep brain stimulation of the subthalamic nuclei induce modulation of emotional processes at different spatial frequencies in Parkinson's disease.

PubMed

Mermillod, Martial; Mondillon, Laurie; Rieu, Isabelle; Devaux, Damien; Chambres, Patrick; Auxiette, Catherine; Dalens, Hélène; Coulangeon, Louise Marie; Jalenques, Isabelle; Durif, Franck

2014-01-01

Deep brain stimulation of the subthalamic nuclei (STN-DBS) is an effective treatment for the most severe forms of Parkinson's disease (PD) and is intended to suppress these patients' motor symptoms. However, be it in association with Dopamine Replacement Therapy (DRT) or not, STN-DBS may in some cases induce addictive or emotional disorders. In the current study, we suggest that PD patients suffer from emotional deficits that have not been revealed in previous studies because in those experiments the stimuli were displayed for a time long enough to allow patients to have recourse to perceptual strategies in order to recognize the emotional facial expressions (EFE). The aim of the current article is to demonstrate the existence of emotional disorders in PD by using a rapid presentation of the visual stimuli (200-ms display time) which curtails their perceptual analysis, and to determine whether STN-DBS, either associated or not associated with DRT, has an impact on the recognition of emotions. The results show that EFE recognition performance depends on both STN-DBS ('on' vs. 'off') and medication ('on' vs. 'off'), but also that these variables have an interactive influence on EFE recognition performance. Moreover, we also reveal how these EFE impairments depend on different spatial frequencies perceptual channels (related to different cortical vs. subcortical neural structures). The effect of PD without therapy seems to be particularly acute for LSF emotional faces, possibly due to a subcortical dysfunction. However, our results indicate that the joint action of STN-DBS and DRT could also disrupt recognition of emotional expressions at the level of occipito-temporal cortical areas (processing HSF visual information) inducing broad global impairment of EFE at the level of HSF visual channels.

Distinct Functional Networks Associated with Improvement of Affective Symptoms and Cognitive Function During Citalopram Treatment in Geriatric Depression

PubMed Central

Diaconescu, Andreea Oliviana; Kramer, Elisse; Hermann, Carol; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David; McIntosh, Anthony Randal; Smith, Gwenn S.

2010-01-01

Variability in the affective and cognitive symptom response to antidepressant treatment has been observed in geriatric depression. The underlying neural circuitry is poorly understood. The current study evaluated the cerebral glucose metabolic effects of citalopram treatment and applied multivariate, functional connectivity analyses to identify brain networks associated with improvements in affective symptoms and cognitive function. Sixteen geriatric depressed patients underwent resting Positron Emission Tomography (PET) studies of cerebral glucose metabolism and assessment of affective symptoms and cognitive function before and after eight weeks of selective serotonin reuptake inhibitor treatment (citalopram). Voxel-wise analyses of the normalized glucose metabolic data showed decreased cerebral metabolism during citalopram treatment in the anterior cingulate gyrus, middle temporal gyrus, precuneus, amygdala, and parahippocampal gyrus. Increased metabolism was observed in the putamen, occipital cortex and cerebellum. Functional connectivity analyses revealed two networks which were uniquely associated with improvement of affective symptoms and cognitive function during treatment. A subcortical-limbic-frontal network was associated with improvement in affect (depression and anxiety), while a medial temporal-parietal-frontal network was associated with improvement in cognition (immediate verbal learning/memory and verbal fluency). The regions that comprise the cognitive network overlap with the regions that are affected in Alzheimer’s dementia. Thus, alterations in specific brain networks associated with improvement of affective symptoms and cognitive function are observed during citalopram treatment in geriatric depression. PMID:20886575

Amyotrophic lateral sclerosis affects cortical and subcortical activity underlying motor inhibition and action monitoring.

PubMed

Mohammadi, Bahram; Kollewe, Katja; Cole, David M; Fellbrich, Anja; Heldmann, Marcus; Samii, Amir; Dengler, Reinhard; Petri, Susanne; Münte, Thomas F; Krämer, Ulrike M

2015-08-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by muscular atrophy, spasticity, and bulbar signs caused by loss of upper and lower motor neurons. Evidence suggests that ALS additionally affects other brain areas including premotor cortex and supplementary motor area. Here, we studied movement execution and inhibition in ALS patients using a stop-signal paradigm and functional magnetic resonance imaging. Seventeen ALS patients and 17 age-matched healthy controls performed a stop-signal task that required responding with a button press to a right- or left-pointing black arrow (go-stimuli). In stop-trials, a red arrow (stop-stimulus) was presented shortly after the black arrow indicating to withhold the prepared movement. Patients had by trend higher reaction times in go-trials but did not differ significantly in their inhibition performance. Patients showed stronger inhibition-related activity in inferior, superior, and middle frontal gyri as well as in putamen and pallidum. Error-related activity, conversely, was found to be stronger in healthy controls, particularly in the insula bilaterally. Patients also showed increased activity in the motor cortex during button presses. The results provide evidence for altered prefrontal and subcortical networks underlying motor execution, motor inhibition, and error monitoring in ALS. © 2015 Wiley Periodicals, Inc.

Early neuroimaging markers of FOXP2 intragenic deletion.

PubMed

Liégeois, Frédérique J; Hildebrand, Michael S; Bonthrone, Alexandra; Turner, Samantha J; Scheffer, Ingrid E; Bahlo, Melanie; Connelly, Alan; Morgan, Angela T

2016-10-13

FOXP2 is the major gene associated with severe, persistent, developmental speech and language disorders. While studies in the original family in which a FOXP2 mutation was found showed volume reduction and reduced activation in core language and speech networks, there have been no imaging studies of different FOXP2 mutations. We conducted a multimodal MRI study in an eight-year-old boy (A-II) with a de novo FOXP2 intragenic deletion. A-II showed marked bilateral volume reductions in the hippocampus, thalamus, globus pallidus, and caudate nucleus compared with 26 control males (effect sizes from -1 to -3). He showed no detectable functional MRI activity when repeating nonsense words. The hippocampus is implicated for the first time in FOXP2 diseases. We conclude that FOXP2 anomaly is either directly or indirectly associated with atypical development of widespread subcortical networks early in life.

Clustered functional MRI of overt speech production.

PubMed

Sörös, Peter; Sokoloff, Lisa Guttman; Bose, Arpita; McIntosh, Anthony R; Graham, Simon J; Stuss, Donald T

2006-08-01

To investigate the neural network of overt speech production, event-related fMRI was performed in 9 young healthy adult volunteers. A clustered image acquisition technique was chosen to minimize speech-related movement artifacts. Functional images were acquired during the production of oral movements and of speech of increasing complexity (isolated vowel as well as monosyllabic and trisyllabic utterances). This imaging technique and behavioral task enabled depiction of the articulo-phonologic network of speech production from the supplementary motor area at the cranial end to the red nucleus at the caudal end. Speaking a single vowel and performing simple oral movements involved very similar activation of the cortical and subcortical motor systems. More complex, polysyllabic utterances were associated with additional activation in the bilateral cerebellum, reflecting increased demand on speech motor control, and additional activation in the bilateral temporal cortex, reflecting the stronger involvement of phonologic processing.

Oxytocin And Vasopressin Modulation Of The Neural Correlates Of Motivation And Emotion: Results From Functional MRI Studies In Awake Rats

PubMed Central

Febo, Marcelo; Ferris, Craig F.

2014-01-01

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. PMID:24486356

Mapping Resting-State Brain Networks in Conscious Animals

PubMed Central

Zhang, Nanyin; Rane, Pallavi; Huang, Wei; Liang, Zhifeng; Kennedy, David; Frazier, Jean A.; King, Jean

2010-01-01

In the present study we mapped brain functional connectivity in the conscious rat at the “resting state” based on intrinsic blood-oxygenation-level dependent (BOLD) fluctuations. The conscious condition eliminated potential confounding effects of anesthetic agents on the connectivity between brain regions. Indeed, using correlational analysis we identified multiple cortical and subcortical regions that demonstrated temporally synchronous variation with anatomically well-defined regions that are crucial to cognitive and emotional information processing including the prefrontal cortex (PFC), thalamus and retrosplenial cortex. The functional connectivity maps created were stringently validated by controlling for false positive detection of correlation, the physiologic basis of the signal source, as well as quantitatively evaluating the reproducibility of maps. Taken together, the present study has demonstrated the feasibility of assessing functional connectivity in conscious animals using fMRI and thus provided a convenient and non-invasive tool to systematically investigate the connectional architecture of selected brain networks in multiple animal models. PMID:20382183

Differences in hemispherical thalamo-cortical causality analysis during resting-state fMRI.

PubMed

Anwar, Abdul Rauf; Muthalib, Makii; Perrey, Stephane; Wolff, Stephan; Deuschl, Guunther; Heute, Ulrich; Muthuraman, Muthuraman

2014-01-01

Thalamus is a very important part of the human brain. It has been reported to act as a relay for the messaging taking place between the cortical and sub-cortical regions of the brain. In the present study, we analyze the functional network between both hemispheres of the brain with the focus on thalamus. We used conditional Granger causality (CGC) and time-resolved partial directed coherence (tPDC) to investigate the functional connectivity. Results of CGC analysis revealed the asymmetry between connection strengths of the bilateral thalamus. Upon testing the functional connectivity of the default-mode network (DMN) at low-frequency fluctuations (LFF) and comparing coherence vectors using Spearman's rank correlation, we found that thalamus is a better source for the signals directed towards the contralateral regions of the brain, however, when thalamus acts as sink, it is a better sink for signals generated from ipsilateral regions of the brain.

Adaptation disrupts motion integration in the primate dorsal stream

PubMed Central

Patterson, Carlyn A.; Wissig, Stephanie C.; Kohn, Adam

2014-01-01

Summary Sensory systems adjust continuously to the environment. The effects of recent sensory experience—or adaptation—are typically assayed by recording in a relevant subcortical or cortical network. However, adaptation effects cannot be localized to a single, local network. Adjustments in one circuit or area will alter the input provided to others, with unclear consequences for computations implemented in the downstream circuit. Here we show that prolonged adaptation with drifting gratings, which alters responses in the early visual system, impedes the ability of area MT neurons to integrate motion signals in plaid stimuli. Perceptual experiments reveal a corresponding loss of plaid coherence. A simple computational model shows how the altered representation of motion signals in early cortex can derail integration in MT. Our results suggest that the effects of adaptation cascade through the visual system, derailing the downstream representation of distinct stimulus attributes. PMID:24507198

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

PubMed Central

Ramsey, Lenny E.; Metcalf, Nicholas V.; Chacko, Ravi V.; Weinberger, Kilian; Baldassarre, Antonello; Hacker, Carl D.; Shulman, Gordon L.; Corbetta, Maurizio

2016-01-01

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain–behavior relationships in stroke. PMID:27402738

Early neurovascular dysfunction in a transgenic rat model of Alzheimer's disease.

PubMed

Joo, Illsung L; Lai, Aaron Y; Bazzigaluppi, Paolo; Koletar, Margaret M; Dorr, Adrienne; Brown, Mary E; Thomason, Lynsie A M; Sled, John G; McLaurin, JoAnne; Stefanovic, Bojana

2017-04-12

Alzheimer's disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans.

Compensatory Motor Network Connectivity is Associated with Motor Sequence Learning after Subcortical Stroke

PubMed Central

Wadden, Katie P.; Woodward, Todd S.; Metzak, Paul D.; Lavigne, Katie M.; Lakhani, Bimal; Auriat, Angela M.; Boyd, Lara A.

2015-01-01

Following stroke, functional networks reorganize and the brain demonstrates widespread alterations in cortical activity. Implicit motor learning is preserved after stroke. However the manner in which brain reorganization occurs, and how it supports behaviour within the damaged brain remains unclear. In this functional magnetic resonance imaging (fMRI) study, we evaluated whole brain patterns of functional connectivity during the performance of an implicit tracking task at baseline and retention, following 5 days of practice. Following motor practice, a significant difference in connectivity within a motor network, consisting of bihemispheric activation of the sensory and motor cortices, parietal lobules, cerebellar and occipital lobules, was observed at retention. Healthy subjects demonstrated greater activity within this motor network during sequence learning compared to random practice. The stroke group did not show the same level of functional network integration, presumably due to the heterogeneity of functional reorganization following stroke. In a secondary analysis, a binary mask of the functional network activated from the aforementioned whole brain analyses was created to assess within-network connectivity, decreasing the spatial distribution and large variability of activation that exists within the lesioned brain. The stroke group demonstrated reduced clusters of connectivity within the masked brain regions as compared to the whole brain approach. Connectivity within this smaller motor network correlated with repeated sequence performance on the retention test. Increased functional integration within the motor network may be an important neurophysiological predictor of motor learning-related change in individuals with stroke. PMID:25757996

Minimum spanning tree analysis of the human connectome

PubMed Central

Sommer, Iris E.; Bohlken, Marc M.; Tewarie, Prejaas; Draaisma, Laurijn; Zalesky, Andrew; Di Biase, Maria; Brown, Jesse A.; Douw, Linda; Otte, Willem M.; Mandl, René C.W.; Stam, Cornelis J.

2018-01-01

Abstract One of the challenges of brain network analysis is to directly compare network organization between subjects, irrespective of the number or strength of connections. In this study, we used minimum spanning tree (MST; a unique, acyclic subnetwork with a fixed number of connections) analysis to characterize the human brain network to create an empirical reference network. Such a reference network could be used as a null model of connections that form the backbone structure of the human brain. We analyzed the MST in three diffusion‐weighted imaging datasets of healthy adults. The MST of the group mean connectivity matrix was used as the empirical null‐model. The MST of individual subjects matched this reference MST for a mean 58%–88% of connections, depending on the analysis pipeline. Hub nodes in the MST matched with previously reported locations of hub regions, including the so‐called rich club nodes (a subset of high‐degree, highly interconnected nodes). Although most brain network studies have focused primarily on cortical connections, cortical–subcortical connections were consistently present in the MST across subjects. Brain network efficiency was higher when these connections were included in the analysis, suggesting that these tracts may be utilized as the major neural communication routes. Finally, we confirmed that MST characteristics index the effects of brain aging. We conclude that the MST provides an elegant and straightforward approach to analyze structural brain networks, and to test network topological features of individual subjects in comparison to empirical null models. PMID:29468769

Regional atrophy of the basal ganglia and thalamus in idiopathic generalized epilepsy.

PubMed

Du, Hanjian; Zhang, Yuanchao; Xie, Bing; Wu, Nan; Wu, Guocai; Wang, Jian; Jiang, Tianzi; Feng, Hua

2011-04-01

To determine the regional changes in the shapes of subcortical structures in idiopathic generalized epilepsy using a vertex-based analysis method. Earlier studies found that gray matter volume in the frontal, parietal, and temporal lobes is significantly altered in idiopathic generalized epilepsy (IGE). Research has indicated that a relationship exists between the brain's subcortical structures and epilepsy. However, little is known about possible changes in the subcortical structures in IGE. This study aims to determine the changes in the shape of subcortical structures in IGE using vertex analysis. Fourteen male patients with IGE and 28 age- and sex-matched healthy controls were included in this study, which used high-resolution magnetic resonance imaging. We performed a vertex-based shape analysis, in which we compared patients with IGE with the controls, on the subcortical structures that we had obtained from the MRI data. Statistical analysis showed significant regional atrophy in the left thalamus, left putamen and bilateral globus pallidus in patients with IGE. These results indicate that regional atrophy of the basal ganglia and the thalamus may be related to seizure disorder. In the future, these findings may prove useful for choosing new therapeutic regimens. Copyright © 2011 Wiley-Liss, Inc.

Changes in subcortical shape and cognitive function in patients with chronic insomnia.

PubMed

Koo, Dae Lim; Shin, Jeong-Hyeon; Lim, Jae-Sung; Seong, Joon-Kyung; Joo, Eun Yeon

2017-07-01

The aim of this study was to examine morphological changes in subcortical structures via surface-based analysis and to correlate local shape changes with cognitive function. We analyzed subcortical brain morphology and compared the shape changes with clinical and neuropsychological features in patients with chronic insomnia. Hippocampal atrophy was associated with higher Pittsburgh Sleep Quality Index scores (r = -0.4, p = 0.0408) and higher arousal indices (r = -0.4, p = 0.0332). Local volume loss of the putamen was associated with higher arousal indices (r = -0.5, p = 0.0416). Atrophic change of subcortical structures including the hippocampus, amygdala, basal ganglia, and thalamus, correlated negatively with verbal fluency, frontal function, verbal memory, and visual memory, respectively, in these patients (|r| ≥ 0.3, p < 0.05). This study shows that sleep quality and fragmentation are closely related to atrophic changes in hippocampus and putamen. In addition, atrophic changes in global subcortical structures are associated with impaired cognitive function in patients with chronic insomnia. Copyright © 2017. Published by Elsevier B.V.

[Is it still the "royal way"? The dream as a junction of neurobiology and psychoanalysis].

PubMed

Simon, Mária

2011-01-01

Some decades ago the dream seemed to be randomly generated by brain stem mechanisms in the cortical and subcortical neuronal networks. However, most recent empirical data, studies on brain lesions and functional neuroimaging results have refuted this theory. Several data support that motivation pathways, memory systems, especially implicit, emotional memory play an important role in dream formation. This essay reviews how the results of neurobiology and cognitive psychology can be fitted into the theoretical frameworks and clinical practice of the psychoanalysis. The main aim is to demonstrate that results of neurobiology and empirical observations of psychoanalysis are complementary rather than contradictory.

Deformed Subcortical Structures Are Related to Past HIV Disease Severity in Youth With Perinatally Acquired HIV Infection.

PubMed

Lewis-de Los Angeles, C Paula; Alpert, Kathryn I; Williams, Paige L; Malee, Kathleen; Huo, Yanling; Csernansky, John G; Yogev, Ram; Van Dyke, Russell B; Sowell, Elizabeth R; Wang, Lei

2016-12-01

Combination antiretroviral therapy has led to increased survival among youth with perinatally acquired HIV (PHIV). However, cognitive deficits continue to be common. Histopathological studies in adults have found HIV concentrated in subcortical structures, which are involved in sensory processing, movement, and higher-order cognition that emerges with development. We conducted magnetic resonance imaging and cognitive testing in 40 youth with PHIV at one site of the Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study. We collected HIV disease-severity measures and substance-use reports. Subcortical volume and shape deformation were generated with FreeSurfer-Initiated Large Deformation Diffeomorphic Metric Mapping. Inward shape deformation was defined as negative displacement. We evaluated associations of subcortical shape deformation with past HIV severity after adjustment for sex, age at neuroimaging, age at HIV severity marker, and substance use. We examined associations between subcortical deformation and cognitive function. Negative correlations between shape deformation and peak HIV viral load (VL) were found in clusters in the caudate tail, globus pallidus, lateral putamen, and anterior and medial thalamus. Positive correlations between shape deformation and nadir CD4-positive T-lymphocyte percentage (CD4%) were found in clusters in the medial and posterior thalamus. Inward deformation in caudate and thalamic clusters correlated with worse cognition. Youth with PHIV have demonstrable subcortical shape deformation related to past HIV severity and cognition; inward deformation was associated with higher peak VL, lower nadir CD4%, and worse cognition. Identifying subcortical deformation may inform clinical practice for early intervention to help improve cognitive outcomes and assess the neuroefficacy of combination antiretroviral therapy in youth with PHIV. © The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

White matter hyperintensity patterns in cerebral amyloid angiopathy and hypertensive arteriopathy.

PubMed

Charidimou, Andreas; Boulouis, Gregoire; Haley, Kellen; Auriel, Eitan; van Etten, Ellis S; Fotiadis, Panagiotis; Reijmer, Yael; Ayres, Alison; Vashkevich, Anastasia; Dipucchio, Zora Y; Schwab, Kristin M; Martinez-Ramirez, Sergi; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M; Gurol, M Edip

2016-02-09

To identify different white matter hyperintensity (WMH) patterns between 2 hemorrhage-prone cerebral small vessel diseases (SVD): cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA). Consecutive patients with SVD-related intracerebral hemorrhage (ICH) from a single-center prospective cohort were analyzed. Four predefined subcortical WMH patterns were compared between the CAA and HA groups. These WMH patterns were (1) multiple subcortical spots; (2) peri-basal ganglia (BG); (3) large posterior subcortical patches; and (4) anterior subcortical patches. Their associations with other imaging (cerebral microbleeds [CMBs], enlarged perivascular spaces [EPVS]) and clinical markers of SVD were investigated using multivariable logistic regression. The cohort included 319 patients with CAA and 137 patients with HA. Multiple subcortical spots prevalence was higher in the CAA compared to the HA group (29.8% vs 16.8%; p = 0.004). Peri-BG WMH pattern was more common in the HA- vs the CAA-ICH group (19% vs 7.8%; p = 0.001). In multivariable logistic regression, presence of multiple subcortical spots was associated with lobar CMBs (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.01-1.50, p = 0.039) and high degree of centrum semiovale EPVS (OR 2.43; 95% CI 1.56-3.80, p < 0.0001). By contrast, age (OR 1.05; 95% CI 1.02-1.09, p = 0.002), deep CMBs (OR 2.46; 95% CI 1.44-4.20, p = 0.001), total WMH volume (OR 1.02; 95% CI 1.01-1.04, p = 0.002), and high BG EPVS degree (OR 8.81; 95% CI 3.37-23.02, p < 0.0001) were predictors of peri-BG WMH pattern. Different patterns of subcortical leukoaraiosis visually identified on MRI might provide insights into the dominant underlying microangiopathy type as well as mechanisms of tissue injury in patients with ICH. © 2016 American Academy of Neurology.

Artificial neural network models for prediction of cardiovascular autonomic dysfunction in general Chinese population

PubMed Central

2013-01-01

Background The present study aimed to develop an artificial neural network (ANN) based prediction model for cardiovascular autonomic (CA) dysfunction in the general population. Methods We analyzed a previous dataset based on a population sample consisted of 2,092 individuals aged 30–80 years. The prediction models were derived from an exploratory set using ANN analysis. Performances of these prediction models were evaluated in the validation set. Results Univariate analysis indicated that 14 risk factors showed statistically significant association with CA dysfunction (P < 0.05). The mean area under the receiver-operating curve was 0.762 (95% CI 0.732–0.793) for prediction model developed using ANN analysis. The mean sensitivity, specificity, positive and negative predictive values were similar in the prediction models was 0.751, 0.665, 0.330 and 0.924, respectively. All HL statistics were less than 15.0. Conclusion ANN is an effective tool for developing prediction models with high value for predicting CA dysfunction among the general population. PMID:23902963

Structural Connectivity Networks of Transgender People

PubMed Central

Hahn, Andreas; Kranz, Georg S.; Küblböck, Martin; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.; Lanzenberger, Rupert

2015-01-01

Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased intrahemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity. PMID:25217469

A Case of Generalized Auditory Agnosia with Unilateral Subcortical Brain Lesion

PubMed Central

Suh, Hyee; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

2012-01-01

The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia. PMID:23342322

Effects of neurological damage on production of formulaic language

PubMed Central

Sidtis, D.; Canterucci, G.; Katsnelson, D.

2014-01-01

Early studies reported preserved formulaic language in left hemisphere damaged subjects and reduced incidence of formulaic expressions in the conversational speech of stroke patients with right hemispheric damage. Clinical observations suggest a possible role also of subcortical nuclei. This study examined formulaic language in the spontaneous speech of stroke patients with left, right, or subcortical damage. Four subjects were interviewed and their speech samples compared to normal speakers. Raters classified formulaic expressions as speech formulae, fillers, sentence stems, and proper nouns. Results demonstrated that brain damage affected novel and formulaic language competence differently, with a significantly smaller proportion of formulaic expressions in subjects with right or subcortical damage compared to left hemisphere damaged or healthy speakers. These findings converge with previous studies that support the proposal of a right hemisphere/subcortical circuit in the management of formulaic expressions, based on a dual-process model of language incorporating novel and formulaic language use. PMID:19382014

Improvement of postoperative cognitive dysfunction and attention network function of patients with ischemic cerebrovascular disease via dexmedetomidine.

PubMed

Zhang, Jingchao; Wang, Guoliang; Zhang, Fangxiang; Zhao, Qian

2018-03-01

The protective effect of dexmedetomidine on cognitive dysfunction and decreased attention network function of patients with ischemic cerebrovascular disease after stenting was investigated. Fifty-eight patients with ischemic cerebrovascular disease undergoing stenting in Guizhou Provincial People's Hospital were selected and randomly divided into control group (n=29) and dexmedetomidine group (n=29). The dexmedetomidine group was treated with dexmedetomidine before induced anesthesia, while the control group was given the same dose of normal saline; and the normal volunteers of the same age were selected as the normal group (n=29). At 3 days after operation, the levels of serum S100B and nerve growth factor (NGF) in each group were detected using the enzyme-linked immunosorbent assay, and the level of brain-derived neurotrophic factor (BDNF) was detected via western blotting. Montreal cognitive assessment (MoCA) and attention network test (ANT) were performed. Moreover, the cognitive function and attention network function, and the effects of dexmedetomidine on cognitive function and attention network function were evaluated. The concentrations of serum S100B and NGF in dexmedetomidine group was lower than those in control group (P<0.01). The results of western blotting showed that the levels of serum BDNF in control group and dexmedetomidine group were significantly lower than that in normal group (P<0.01), and it was higher in dexmedetomidine group than that in control group (P<0.01). Besides, both MoCA and ANT results revealed that the visual space and executive function scores, attention scores, delayed memory scores, targeted network efficiency and executive control network efficiency in dexmedetomidine group were obviously higher than those in control group (P<0.01). The cognitive function and attention network function of patients with ischemic cerebrovascular disease have a certain degree of damage, and the preoperative administration of dexmedetomidine can effectively improve the patient's cognitive dysfunction and attention network function after operation.

Noradrenergic Dysfunction in Alzheimer's and Parkinson's Diseases-An Overview of Imaging Studies.

PubMed

Peterson, Andrew C; Li, Chiang-Shan R

2018-01-01

Noradrenergic dysfunction contributes to cognitive impairment in Alzheimer's Disease (AD) and Parkinson's Disease (PD). Conventional therapeutic strategies seek to enhance cholinergic and dopaminergic neurotransmission in AD and PD, respectively, and few studies have examined noradrenergic dysfunction as a target for medication development. We review the literature of noradrenergic dysfunction in AD and PD with a focus on human imaging studies that implicate the locus coeruleus (LC) circuit. The LC sends noradrenergic projections diffusely throughout the cerebral cortex and plays a critical role in attention, learning, working memory, and cognitive control. The LC undergoes considerable degeneration in both AD and PD. Advances in magnetic resonance imaging have facilitated greater understanding of how structural and functional alteration of the LC may contribute to cognitive decline in AD and PD. We discuss the potential roles of the noradrenergic system in the pathogenesis of AD and PD with an emphasis on postmortem anatomical studies, structural MRI studies, and functional MRI studies, where we highlight changes in LC connectivity with the default mode network (DMN). LC degeneration may accompany deficient capacity in suppressing DMN activity and increasing saliency and task control network activities to meet behavioral challenges. We finish by proposing potential and new directions of research to address noradrenergic dysfunction in AD and PD.

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

PubMed

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism.

PubMed

Coplan, Jeremy D; Hodulik, Sarah; Mathew, Sanjay J; Mao, Xiangling; Hof, Patrick R; Gorman, Jack M; Shungu, Dikoma C

2011-01-01

We have demonstrated in a previous study that a high degree of worry in patients with generalized anxiety disorder (GAD) correlates positively with intelligence and that a low degree of worry in healthy subjects correlates positively with intelligence. We have also shown that both worry and intelligence exhibit an inverse correlation with certain metabolites in the subcortical white matter. Here we re-examine the relationships among generalized anxiety, worry, intelligence, and subcortical white matter metabolism in an extended sample. Results from the original study were combined with results from a second study to create a sample comprised of 26 patients with GAD and 18 healthy volunteers. Subjects were evaluated using the Penn State Worry Questionnaire, the Wechsler Brief intelligence quotient (IQ) assessment, and proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to measure subcortical white matter metabolism of choline and related compounds (CHO). Patients with GAD exhibited higher IQ's and lower metabolite concentrations of CHO in the subcortical white matter in comparison to healthy volunteers. When data from GAD patients and healthy controls were combined, relatively low CHO predicted both relatively higher IQ and worry scores. Relatively high anxiety in patients with GAD predicted high IQ whereas relatively low anxiety in controls also predicted high IQ. That is, the relationship between anxiety and intelligence was positive in GAD patients but inverse in healthy volunteers. The collective data suggest that both worry and intelligence are characterized by depletion of metabolic substrate in the subcortical white matter and that intelligence may have co-evolved with worry in humans.

Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

PubMed

Pitel, Anne Lise; Segobin, Shailendra H; Ritz, Ludivine; Eustache, Francis; Beaunieux, Hélène

2015-07-01

Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks. Copyright © 2014. Published by Elsevier Ltd.

Coronary microvascular dysfunction in diabetes mellitus

PubMed Central

Selthofer-Relatic, Kristina; Drenjancevic, Ines; Bacun, Tatjana; Bosnjak, Ivica; Kibel, Dijana; Gros, Mario

2017-01-01

The significance, mechanisms and consequences of coronary microvascular dysfunction associated with diabetes mellitus are topics into which we have insufficient insight at this time. It is widely recognized that endothelial dysfunction that is caused by diabetes in various vascular beds contributes to a wide range of complications and exerts unfavorable effects on microcirculatory regulation. The coronary microcirculation is precisely regulated through a number of interconnected physiological processes with the purpose of matching local blood flow to myocardial metabolic demands. Dysregulation of this network might contribute to varying degrees of pathological consequences. This review discusses the most important findings regarding coronary microvascular dysfunction in diabetes from pre-clinical and clinical perspectives. PMID:28643578

Hyperconnectivity in juvenile myoclonic epilepsy: a network analysis.

PubMed

Caeyenberghs, K; Powell, H W R; Thomas, R H; Brindley, L; Church, C; Evans, J; Muthukumaraswamy, S D; Jones, D K; Hamandi, K

2015-01-01

Juvenile myoclonic epilepsy (JME) is a common idiopathic (genetic) generalized epilepsy (IGE) syndrome characterized by impairments in executive and cognitive control, affecting independent living and psychosocial functioning. There is a growing consensus that JME is associated with abnormal function of diffuse brain networks, typically affecting frontal and fronto-thalamic areas. Using diffusion MRI and a graph theoretical analysis, we examined bivariate (network-based statistic) and multivariate (global and local) properties of structural brain networks in patients with JME (N = 34) and matched controls. Neuropsychological assessment was performed in a subgroup of 14 patients. Neuropsychometry revealed impaired visual memory and naming in JME patients despite a normal full scale IQ (mean = 98.6). Both JME patients and controls exhibited a small world topology in their white matter networks, with no significant differences in the global multivariate network properties between the groups. The network-based statistic approach identified one subnetwork of hyperconnectivity in the JME group, involving primary motor, parietal and subcortical regions. Finally, there was a significant positive correlation in structural connectivity with cognitive task performance. Our findings suggest that structural changes in JME patients are distributed at a network level, beyond the frontal lobes. The identified subnetwork includes key structures in spike wave generation, along with primary motor areas, which may contribute to myoclonic jerks. We conclude that analyzing the affected subnetworks may provide new insights into understanding seizure generation, as well as the cognitive deficits observed in JME patients.

Hyperconnectivity in juvenile myoclonic epilepsy: A network analysis

PubMed Central

Caeyenberghs, K.; Powell, H.W.R.; Thomas, R.H.; Brindley, L.; Church, C.; Evans, J.; Muthukumaraswamy, S.D.; Jones, D.K.; Hamandi, K.

2014-01-01

Objective Juvenile myoclonic epilepsy (JME) is a common idiopathic (genetic) generalized epilepsy (IGE) syndrome characterized by impairments in executive and cognitive control, affecting independent living and psychosocial functioning. There is a growing consensus that JME is associated with abnormal function of diffuse brain networks, typically affecting frontal and fronto-thalamic areas. Methods Using diffusion MRI and a graph theoretical analysis, we examined bivariate (network-based statistic) and multivariate (global and local) properties of structural brain networks in patients with JME (N = 34) and matched controls. Neuropsychological assessment was performed in a subgroup of 14 patients. Results Neuropsychometry revealed impaired visual memory and naming in JME patients despite a normal full scale IQ (mean = 98.6). Both JME patients and controls exhibited a small world topology in their white matter networks, with no significant differences in the global multivariate network properties between the groups. The network-based statistic approach identified one subnetwork of hyperconnectivity in the JME group, involving primary motor, parietal and subcortical regions. Finally, there was a significant positive correlation in structural connectivity with cognitive task performance. Conclusions Our findings suggest that structural changes in JME patients are distributed at a network level, beyond the frontal lobes. The identified subnetwork includes key structures in spike wave generation, along with primary motor areas, which may contribute to myoclonic jerks. We conclude that analyzing the affected subnetworks may provide new insights into understanding seizure generation, as well as the cognitive deficits observed in JME patients. PMID:25610771

Structural Connectivity Relates to Perinatal Factors and Functional Impairment at 7 Years in Children Born Very Preterm

PubMed Central

Thompson, Deanne K.; Chen, Jian; Beare, Richard; Adamson, Christopher L.; Ellis, Rachel; Ahmadzai, Zohra M.; Kelly, Claire E.; Lee, Katherine J.; Zalesky, Andrew; Yang, Joseph Y.M.; Hunt, Rodney W.; Cheong, Jeanie L.Y.; Inder, Terrie E.; Doyle, Lex W.; Seal, Marc L.; Anderson, Peter J.

2016-01-01

Objective To use structural connectivity to (1) compare brain networks between typically and atypically developing (very preterm) children, (2) explore associations between potential perinatal developmental disturbances and brain networks, and (3) describe associations between brain networks and functional impairments in very preterm children. Methods 26 full-term and 107 very preterm 7-year-old children (born <30 weeks’ gestational age and/or <1250 g) underwent T1- and diffusion-weighted imaging. Global white matter fiber networks were produced using 80 cortical and subcortical nodes, and edges created using constrained spherical deconvolution-based tractography. Global graph theory metrics were analysed, and regional networks were identified using network-based statistics. Cognitive and motor function were assessed at 7 years of age. Results Compared with full-term children, very preterm children had reduced density, lower global efficiency and higher local efficiency. Those with lower gestational age at birth, infection or higher neonatal brain abnormality score had reduced connectivity. Reduced connectivity within a widespread network was predictive of impaired IQ, while reduced connectivity within the right parietal and temporal lobes was associated with motor impairment in very preterm children. Conclusions This study utilized an innovative structural connectivity pipeline to reveal that children born very preterm have less connected and less complex brain networks compared with typically developing term-born children. Adverse perinatal factors led to disturbances in white matter connectivity, which in turn are associated with impaired functional outcomes, highlighting novel structure-function relationships. PMID:27046108

Atomoxetine restores the response inhibition network in Parkinson's disease.

PubMed

Rae, Charlotte L; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E; Jones, P Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

2016-08-01

Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson's disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson's disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson's disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson's disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Multiple Resting-State Networks Are Associated With Tremors and Cognitive Features in Essential Tremor.

PubMed

Fang, Weidong; Chen, Huiyue; Wang, Hansheng; Zhang, Han; Liu, Mengqi; Puneet, Munankami; Lv, Fajin; Cheng, Oumei; Wang, Xuefeng; Lu, Xiurong; Luo, Tianyou

2015-12-01

The heterogeneous clinical features of essential tremor indicate that the dysfunctions of this syndrome are not confined to motor networks, but extend to nonmotor networks. Currently, these neural network dysfunctions in essential tremor remain unclear. In this study, independent component analysis of resting-state functional MRI was used to study these neural network mechanisms. Thirty-five essential tremor patients and 35 matched healthy controls with clinical and neuropsychological tests were included, and eight resting-state networks were identified. After considering the structure and head-motion factors and testing the reliability of the selected resting-state networks, we assessed the functional connectivity changes within or between resting-state networks. Finally, image-behavior correlation analysis was performed. Compared to healthy controls, essential tremor patients displayed increased functional connectivity in the sensorimotor and salience networks and decreased functional connectivity in the cerebellum network. Additionally, increased functional network connectivity was observed between anterior and posterior default mode networks, and a decreased functional network connectivity was noted between the cerebellum network and the sensorimotor and posterior default mode networks. Importantly, the functional connectivity changes within and between these resting-state networks were correlated with the tremor severity and total cognitive scores of essential tremor patients. The findings of this study provide the first evidence that functional connectivity changes within and between multiple resting-state networks are associated with tremors and cognitive features of essential tremor, and this work demonstrates a potential approach for identifying the underlying neural network mechanisms of this syndrome. © 2015 International Parkinson and Movement Disorder Society.

Model of music cognition and amusia.

PubMed

García-Casares, N; Berthier Torres, M L; Froudist Walsh, S; González-Santos, P

2013-04-01

The study of the neural networks involved in music processing has received less attention than work researching the brain's language networks. For the last two decades there has been a growing interest in discovering the functional mechanisms of the musical brain and understanding those disorders in which brain regions linked with perception and production of music are damaged. Congenital and acquired musical deficits in their various forms (perception, execution, music-memory) are grouped together under the generic term amusia. In this selective review we present the "cutting edge" studies on the cognitive and neural processes implicated in music and the various forms of amusia. Musical processing requires a large cortico-subcortical network which is distributed throughout both cerebral hemispheres and the cerebellum. The analysis of healthy subjects using functional neuroimaging and examination of selective deficits (e.g., tone, rhythm, timbre, melodic contours) in patients will improve our knowledge of the mechanisms involved in musical processing and the latter's relationship with other cognitive processes. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Dopamine precursor depletion impairs structure and efficiency of resting state brain functional networks.

PubMed

Carbonell, Felix; Nagano-Saito, Atsuko; Leyton, Marco; Cisek, Paul; Benkelfat, Chawki; He, Yong; Dagher, Alain

2014-09-01

Spatial patterns of functional connectivity derived from resting brain activity may be used to elucidate the topological properties of brain networks. Such networks are amenable to study using graph theory, which shows that they possess small world properties and can be used to differentiate healthy subjects and patient populations. Of particular interest is the possibility that some of these differences are related to alterations in the dopamine system. To investigate the role of dopamine in the topological organization of brain networks at rest, we tested the effects of reducing dopamine synthesis in 13 healthy subjects undergoing functional magnetic resonance imaging. All subjects were scanned twice, in a resting state, following ingestion of one of two amino acid drinks in a randomized, double-blind manner. One drink was a nutritionally balanced amino acid mixture, and the other was tyrosine and phenylalanine deficient. Functional connectivity between 90 cortical and subcortical regions was estimated for each individual subject under each dopaminergic condition. The lowered dopamine state caused the following network changes: reduced global and local efficiency of the whole brain network, reduced regional efficiency in limbic areas, reduced modularity of brain networks, and greater connection between the normally anti-correlated task-positive and default-mode networks. We conclude that dopamine plays a role in maintaining the efficient small-world properties and high modularity of functional brain networks, and in segregating the task-positive and default-mode networks. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2014 Elsevier Ltd. All rights reserved.

A diffusion modeling approach to understanding contextual cueing effects in children with ADHD.

PubMed

Weigard, Alexander; Huang-Pollock, Cynthia

2014-12-01

Strong theoretical models suggest implicit learning deficits may exist among children with Attention Deficit Hyperactivity Disorder (ADHD). We examine implicit contextual cueing (CC) effects among children with ADHD (n = 72) and non-ADHD Controls (n = 36). Using Ratcliff's drift diffusion model, we found that among Controls, the CC effect is due to improvements in attentional guidance and to reductions in response threshold. Children with ADHD did not show a CC effect; although they were able to use implicitly acquired information to deploy attentional focus, they had more difficulty adjusting their response thresholds. Improvements in attentional guidance and reductions in response threshold together underlie the CC effect. Results are consistent with neurocognitive models of ADHD that posit subcortical dysfunction but intact spatial attention, and encourage the use of alternative data analytic methods when dealing with reaction time data. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Parkinsonism due to manganism in a welder: neurological and neuropsychological sequelae.

PubMed

Bowler, Rosemarie M; Koller, William; Schulz, Paul E

2006-05-01

A 33-year-old welder with 3 years of exposure to manganese (Mn) bearing welding fumes was seen by neurologists for cognitive and motor complaints. He exhibited signs and symptoms of Parkinson's disease, including tremor, bradykinesia, gait disturbance and cogwheel rigidity. However, he was young and had significant inattention and forgetfulness, had found levodopa unhelpful and moved with a cock-walk gait, all of which suggested manganism. His serum and urine levels of Mn were, in fact, elevated, and his brain MRI had increased T1-weighted signal intensities in the basal ganglia bilaterally (globus pallidus) consistent with Mn deposition. Two years later, he underwent comprehensive neuropsychological testing. Clinical history indicated a mild tremor and emotional dysfunction with irritability, anxiety, and depression with psychotic features. He showed deficits in cognitive flexibility, information processing and speed, and greatly reduced motor speed, which are consistent with a fronto-subcortical process. These findings support a diagnosis of early onset parkinsonism from welding.

Brain structure, executive function and appetitive traits in adolescent obesity.

PubMed

de Groot, C J; van den Akker, E L T; Rings, E H H M; Delemarre-van de Waal, H A; van der Grond, J

2017-08-01

Children with obesity show differences in brain structure, executive function and appetitive traits when compared with lean peers. Little is known on the relationship between brain structure and these traits. To investigate the relationship between differences in brain structure and executive function and appetitive traits, in obese and lean adolescents. MRI was used to measure cortical thickness and subcortical volumes. Executive function was measured by a Stop Signal-and a Choice Delay Task. Appetitive traits were measured using the Child Eating Behaviour Questionnaire. Adolescents with obesity had greater volumes of the pallidum; 1.78 mL (SE 0.03, p=0.014), when compared with controls; 1.65 mL (SE 0.02). In the group with obesity, greater pallidum volume was positively associated with the ability to delay reward in the Choice Delay Task (p=0.012). The association between pallidum volumes and Choice Delay Task in obese adolescents supports the hypothesis that the pallidum plays an important role in executive dysfunction in obese children. © 2016 World Obesity Federation.

Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease.

PubMed

Li, Rui; Sun, Le; Fang, Ai; Li, Peng; Wu, Qian; Wang, Xiaoqun

2017-11-01

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.

The developing human brain: age-related changes in cortical, subcortical, and cerebellar anatomy.

PubMed

Sussman, Dafna; Leung, Rachel C; Chakravarty, M Mallar; Lerch, Jason P; Taylor, Margot J

2016-04-01

This study is the first to characterize normal development and sex differences across neuroanatomical structures in cortical, subcortical, and cerebellar brain regions in a single large cohort. One hundred and ninety-two magnetic resonance images were examined from 96 typically developing females and 96 age-matched typically developing males from 4 to 18 years of age. Image segmentation of the cortex was conducted with CIVET, while that of the cerebellum, hippocampi, thalamus, and basal ganglia were conducted using the MAGeT algorithm. Cortical thickness analysis revealed that most cortical regions decrease linearly, while surface area increases linearly with age. Volume relative to total cerebrum followed a quadratic trend with age, with only the left supramarginal gyrus showing sexual dimorphism. Hippocampal relative volume increased linearly, while the thalamus, caudate, and putamen decreased linearly, and the cerebellum did not change with age. The relative volumes of several subcortical subregions followed inverted U-shaped trends that peaked at ~12 years of age. Many subcortical structures were found to be larger in females than in males, independently of age, while others showed a sex-by-age interaction. This study provides a comprehensive assessment of cortical, subcortical, and cerebellar growth patterns during normal development, and draws attention to the role of sex on neuroanatomical maturation throughout childhood and adolescence.

Preferred Tempo and Low-Audio-Frequency Bias Emerge From Simulated Sub-cortical Processing of Sounds With a Musical Beat

PubMed Central

Zuk, Nathaniel J.; Carney, Laurel H.; Lalor, Edmund C.

2018-01-01

Prior research has shown that musical beats are salient at the level of the cortex in humans. Yet below the cortex there is considerable sub-cortical processing that could influence beat perception. Some biases, such as a tempo preference and an audio frequency bias for beat timing, could result from sub-cortical processing. Here, we used models of the auditory-nerve and midbrain-level amplitude modulation filtering to simulate sub-cortical neural activity to various beat-inducing stimuli, and we used the simulated activity to determine the tempo or beat frequency of the music. First, irrespective of the stimulus being presented, the preferred tempo was around 100 beats per minute, which is within the range of tempi where tempo discrimination and tapping accuracy are optimal. Second, sub-cortical processing predicted a stronger influence of lower audio frequencies on beat perception. However, the tempo identification algorithm that was optimized for simple stimuli often failed for recordings of music. For music, the most highly synchronized model activity occurred at a multiple of the beat frequency. Using bottom-up processes alone is insufficient to produce beat-locked activity. Instead, a learned and possibly top-down mechanism that scales the synchronization frequency to derive the beat frequency greatly improves the performance of tempo identification. PMID:29896080

Edge Density Imaging: Mapping the Anatomic Embedding of the Structural Connectome Within the White Matter of the Human Brain

PubMed Central

Owen, Julia P.; Chang, Yi-Shin; Mukherjee, Pratik

2015-01-01

The structural connectome has emerged as a powerful tool to characterize the network architecture of the human brain and shows great potential for generating important new biomarkers for neurologic and psychiatric disorders. The edges of the cerebral graph traverse white matter to interconnect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Mapping the paths of the connectome edges could elucidate the relative importance of individual white matter tracts to the overall network topology of the brain and also lead to a better understanding of the effect of regionally-specific white matter pathology on cognition and behavior. In this work, we introduce edge density imaging (EDI), which maps the number of network edges that pass through every white matter voxel. Test-retest analysis shows good to excellent reliability for edge density (ED) measurements, with consistent results using different cortical and subcortical parcellation schemes and different diffusion MR imaging acquisition parameters. We also demonstrate that ED yields complementary information to both traditional and emerging voxel-wise metrics of white matter microstructure and connectivity, including fractional anisotropy, track density, fiber orientation dispersion and neurite density. Our results demonstrate spatially ordered variations of ED throughout the white matter, notably including greater ED in posterior than anterior cerebral white matter. The EDI framework is employed to map the white matter regions that are enriched with pathways connecting rich club nodes and also those with high densities of intra-modular and inter-modular edges. We show that periventricular white matter has particularly high ED and high densities of rich club edges, which is significant for diseases in which these areas are selectively affected, ranging from white matter injury of prematurity in infants to leukoaraiosis in the elderly. Using edge betweenness centrality, we identify specific white matter regions involved in a large number of shortest paths, some containing highly connected rich club edges while others are relatively isolated within individual modules. Overall, these findings reveal an intricate relationship between white matter anatomy and the structural connectome, motivating further exploration of EDI for biomarkers of cognition and behavior. PMID:25592996

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

PubMed Central

Peters, Sarah K.; Dunlop, Katharine; Downar, Jonathan

2016-01-01

The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network’s associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN’s cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders. PMID:28082874

Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex

PubMed Central

Friedman, Amy L.; Burgess, Ashley; Ramaseshan, Karthik; Easter, Phil; Khatib, Dalal; Chowdury, Asadur; Arnold, Paul D.; Hanna, Gregory L.; Rosenberg, David R.; Diwadkar, Vaibhav A.

2017-01-01

In an effort to elucidate differences in functioning brain networks between youth with obsessive-compulsive disorder and controls, we used fMRI signals to analyze brain network interactions of the dorsal anterior cingulate cortex (dACC) during visually coordinated motor responses. Subjects made a uni-manual response to briefly presented probes, at periodic (allowing participants to maintain a “motor set”) or random intervals (demanding reactive responses). Network interactions were assessed using psycho-physiological interaction (PPI), a basic model of functional connectivity evaluating modulatory effects of the dACC in the context of each task condition. Across conditions, OCD were characterized by hyper-modulation by the dACC, with loci alternatively observed as both condition-general and condition-specific. Thus, dynamically driven task demands during simple uni-manual motor control induce compensatory network interactions in cortical-thalamic regions in OCD. These findings support previous research in OCD showing compensatory network interactions during complex memory tasks, but establish that these network effects are observed during basic sensorimotor processing. Thus, these patterns of network dysfunction may in fact be independent of the complexity of tasks used to induce brain network activity. Hypothesis-driven approaches coupled with sophisticated network analyses are a highly valuable approach in using fMRI to uncover mechanisms in disorders like OCD. PMID:27992792

Precortical phase of Alzheimer’s disease (AD)-related tau cytoskeletal pathology

PubMed Central

Stratmann, Katharina; Heinsen, Helmut; Korf, Horst-Werner; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; Bouzrou, Mohamed; Grinberg, Lea T.; Bohl, Jürgen; Wharton, Stephen B; den Dunnen, Wilfred; Rüb, Udo

2015-01-01

Alzheimer’s disease (AD) represents the most frequent progressive neuropsychiatric disorder worldwide leading to dementia and accounts for 60 to 70% of demented individuals. In view of the early appearance of neuronal deposits of the hyperphosphorylated cytoskeletal protein tau in the transentorhinal and entorhinal regions of the allocortex (i.e. in Braak and Braak AD stage I in the evolution of the AD-related cortical tau cytoskeletal pathology) it has been believed for a long time that these allocortical regions represent the first brain targets of the AD-related tau cytoskeletal pathology. However, recent pathoanatomical studies suggested that the subcortical brain nuclei that send efferent projections to the transentorhinal and entorhinal regions may also comprise AD-related cytoskeletal changes already at very early Braak and Braak AD stages. In order to corroborate these initial results we systematically investigated the presence and extent of the AD-related cytoskeletal pathology in serial thick tissue sections through all the subcortical nuclei known to send efferent projections to these vulnerable allocortical regions of three individuals with Braak and Braak AD stage 0 and fourteen individuals with Braak and Braak AD stage I by means of immunostainings with the anti-tau antibody AT8. These investigations revealed consistent AT8 immunoreactive neuronal tau cytoskeletal pathology in a subset of these subcortical nuclei (i.e. medial septal nucleus, nuclei of the vertical and horizontal limbs of the diagonal band of Broca, basal nucleus of Meynert; claustrum; hypothalamic ventromedial, tuberomamillary and supramamillary nuclei, perifornical region and lateral area; thalamic central medial, laterodorsal, subparafascicular, and central lateral nuclei, medial pulvinar and limitans-suprageniculate complex; peripeduncular nucleus, dopaminergic substantia nigra and ventral tegmental area, periaqueductal gray, midbrain and pontine dorsal raphe nuclei, locus coeruleus, and parabrachial nuclei) in the Braak and Braak AD stage 0 individuals and in all of these subcortical nuclei in the Braak and Braak AD stage I individuals. The widespread affection of the subcortical nuclei in our Braak and Braak AD stage I individuals shows that the extent of the subcortical tau cytoskeletal pathology in this AD stage has been considerably underestimated during the last decades. In addition, our novel findings in the Braak and Braak AD stage 0 individuals support the concept that subcortical nuclei become already affected during an early ‘pre-cortical’ evolutional phase before the first AD-related cytoskeletal changes occur in the well-known cortical predilection sites of the mediobasal temporal lobe (i.e. transentorhinal and entorhinal regions). In addition, our new findings indicate that the AD-related tau cytoskeletal pathology by no means is confined to single subcortical nuclei of Braak and Braak AD stage 0 individuals, but may develop in a large variety of their subcortical nuclei interconnected with the allocortical entorhinal and transentorhinal regions. Accordingly, these very early involved subcortical brain regions may represent the origin of the AD-related tau cytoskeletal pathology, from where the neuronal cytoskeletal pathology takes an ascending course towards the secondarily affected allocortex and spreads transneuronally along anatomical pathways and interconnectivities in predictable and stereotypical sequences PMID:26193084

Brain networks during free viewing of complex erotic movie: new insights on psychogenic erectile dysfunction.

PubMed

Cera, Nicoletta; Di Pierro, Ezio Domenico; Ferretti, Antonio; Tartaro, Armando; Romani, Gian Luca; Perrucci, Mauro Gianni

2014-01-01

Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA) and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC), using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN), default-mode network (DMN), fronto-parietal network (FPN) and salience network (SN) were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other's actions. Moreover, the between group differences in the SN nodes suggested a decreased recognition of autonomical and sexual arousal changes in EDp.

Divergent functional connectivity during attentional processing in Lewy body dementia and Alzheimer's disease.

PubMed

Kobeleva, Xenia; Firbank, Michael; Peraza, Luis; Gallagher, Peter; Thomas, Alan; Burn, David J; O'Brien, John; Taylor, John-Paul

2017-07-01

Attention and executive dysfunction are features of Lewy body dementia (LBD) but their neuroanatomical basis is poorly understood. To investigate underlying dysfunctional attention-executive network (EXEC) interactions, we examined functional connectivity (FC) in 30 patients with LBD, 20 patients with Alzheimer's disease (AD), and 21 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Participants performed a modified Attention Network Test (ANT), where they were instructed to press a button in response to the majority direction of arrows, which were either all pointing in the same direction or with one pointing in the opposite direction. Network activations during both target conditions and a baseline condition (no target) were derived by (ICA) Independent Component Analysis, and interactions between these networks were examined using the beta series correlations approach. Our study revealed that FC of ventral and dorsal attention networks DAN was reduced in LBD during all conditions, although most prominently during incongruent trials. These alterations in connectivity might be driven by a failure of engagement of ventral attention networks, and consequent over-reliance on the DAN. In contrast, when comparing AD patients with the other groups, we found hyperconnectivity between the posterior part of the default mode network (DMN) and the DAN in all conditions, particularly during incongruent trials. This might be attributable to either a compensatory effect to overcome DMN dysfunction, or be arising as a result of a disturbed transition of the DMN from rest to task. Our results demonstrate that dementia syndromes can be characterized both by hyper- and hypoconnectivity of distinct brain networks, depending on the interplay between task demand and available cognitive resources. However these are dependent upon the underlying pathology, which needs to be taken into account when developing specific cognitive therapies for LBD as compared to Alzheimer's. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Brain Networks during Free Viewing of Complex Erotic Movie: New Insights on Psychogenic Erectile Dysfunction

PubMed Central

Cera, Nicoletta; Di Pierro, Ezio Domenico; Ferretti, Antonio; Tartaro, Armando; Romani, Gian Luca; Perrucci, Mauro Gianni

2014-01-01

Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA) and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC), using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN), default-mode network (DMN), fronto-parietal network (FPN) and salience network (SN) were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other’s actions. Moreover, the between group differences in the SN nodes suggested a decreased recognition of autonomical and sexual arousal changes in EDp. PMID:25126947

A neural model of mechanisms of empathy deficits in narcissism

PubMed Central

Jankowiak-Siuda, Kamila; Zajkowski, Wojciech

2013-01-01

From a multidimensional perspective, empathy is a process that includes affective sharing and imagining and understanding the emotions of others. The primary brain structures involved in mediating the components of empathy are the anterior insula (AI), the anterior cingulate cortex (ACC), and specific regions of the medial prefrontal cortex (MPFC). The AI and ACC are the main nodes in the salience network (SN), which selects and coordinates the information flow from the intero- and exteroreceptors. AI might play a role as a crucial hub – a dynamic switch between 2 separate networks of cognitive processing: the central executive network (CEN), which is concerned with effective task execution, and the default mode network (DMN), which is involved with self-reflective processes. Given various classifications, a deficit in empathy may be considered a central dysfunctional trait in narcissism. A recent fMRI study suggests that deficit in empathy is due to a dysfunction in the right AI. Based on the acquired data, we propose a theoretical model of imbalanced SN functioning in narcissism in which the dysfunctional AI hub is responsible for constant DMN activation, which, in turn, centers one’s attention on the self. This might hinder the ability to affectively share and understand the emotions of others. This review paper on neural mechanisms of empathy deficits in narcissism aims to inspire and direct future research in this area. PMID:24189465

Early neurovascular dysfunction in a transgenic rat model of Alzheimer’s disease

PubMed Central

Joo, Illsung L.; Lai, Aaron Y.; Bazzigaluppi, Paolo; Koletar, Margaret M.; Dorr, Adrienne; Brown, Mary E.; Thomason, Lynsie A. M.; Sled, John G.; McLaurin, JoAnne; Stefanovic, Bojana

2017-01-01

Alzheimer’s disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans. PMID:28401931

Brain imaging research in autism spectrum disorders: in search of neuropathology and health across the lifespan.

PubMed

Lainhart, Janet E

2015-03-01

Advances in brain imaging research in autism spectrum disorders (ASD) are rapidly occurring, and the amount of neuroimaging research has dramatically increased over the past 5 years. In this review, advances during the past 12 months and longitudinal studies are highlighted. Cross-sectional neuroimaging research provides evidence that the neural underpinnings of the behavioral signs of ASD involve not only dysfunctional integration of information across distributed brain networks but also basic dysfunction in primary cortices.Longitudinal studies of ASD show abnormally enlarged brain volumes and increased rates of brain growth during early childhood in only a small minority of ASD children. There is evidence of disordered development of white matter microstructure and amygdala growth, and at 2 years of age, network inefficiencies in posterior cerebral regions.From older childhood into adulthood, atypical age-variant and age-invariant changes in the trajectories of total and regional brain volumes and cortical thickness are apparent at the group level. There is evidence of abnormalities in posterior lobes and posterior brain networks during the first 2 years of life in ASD and, even in older children and adults, dysfunction in primary cortical areas.

An improved FSL-FIRST pipeline for subcortical gray matter segmentation to study abnormal brain anatomy using quantitative susceptibility mapping (QSM).

PubMed

Feng, Xiang; Deistung, Andreas; Dwyer, Michael G; Hagemeier, Jesper; Polak, Paul; Lebenberg, Jessica; Frouin, Frédérique; Zivadinov, Robert; Reichenbach, Jürgen R; Schweser, Ferdinand

2017-06-01

Accurate and robust segmentation of subcortical gray matter (SGM) nuclei is required in many neuroimaging applications. FMRIB's Integrated Registration and Segmentation Tool (FIRST) is one of the most popular software tools for automated subcortical segmentation based on T 1 -weighted (T1w) images. In this work, we demonstrate that FIRST tends to produce inaccurate SGM segmentation results in the case of abnormal brain anatomy, such as present in atrophied brains, due to a poor spatial match of the subcortical structures with the training data in the MNI space as well as due to insufficient contrast of SGM structures on T1w images. Consequently, such deviations from the average brain anatomy may introduce analysis bias in clinical studies, which may not always be obvious and potentially remain unidentified. To improve the segmentation of subcortical nuclei, we propose to use FIRST in combination with a special Hybrid image Contrast (HC) and Non-Linear (nl) registration module (HC-nlFIRST), where the hybrid image contrast is derived from T1w images and magnetic susceptibility maps to create subcortical contrast that is similar to that in the Montreal Neurological Institute (MNI) template. In our approach, a nonlinear registration replaces FIRST's default linear registration, yielding a more accurate alignment of the input data to the MNI template. We evaluated our method on 82 subjects with particularly abnormal brain anatomy, selected from a database of >2000 clinical cases. Qualitative and quantitative analyses revealed that HC-nlFIRST provides improved segmentation compared to the default FIRST method. Copyright © 2017 Elsevier Inc. All rights reserved.

Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems.

PubMed

Schmahmann, Jeremy D; Pandya, Deepak N

2008-09-01

Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion. First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes. We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model enables the formulation and testing of future hypotheses in investigations using evolving magnetic resonance imaging techniques in humans, and in clinical studies in patients with cortical and subcortical lesions.

Continuous physical examination during subcortical resection in awake craniotomy patients: Its usefulness and surgical outcome.

PubMed

Bunyaratavej, Krishnapundha; Sangtongjaraskul, Sunisa; Lerdsirisopon, Surunchana; Tuchinda, Lawan

2016-08-01

To evaluate the value of physical examination as a monitoring tool during subcortical resection in awake craniotomy patients and surgical outcomes. Authors reviewed medical records of patients underwent awake craniotomy with continuous physical examination for pathology adjacent to the eloquent area. Between January 2006 and August 2015, there were 37 patients underwent awake craniotomy with continuous physical examination. Pathology was located in the left cerebral hemisphere in 28 patients (75.7%). Thirty patients (81.1%) had neuroepithelial tumors. Degree of resections were defined as total, subtotal, and partial in 16 (43.2%), 11 (29.7%) and 10 (27.0%) patients, respectively. Median follow up duration was 14 months. The reasons for termination of subcortical resection were divided into 3 groups as follows: 1) by anatomical landmark with the aid of neuronavigation in 20 patients (54%), 2) by reaching subcortical stimulation threshold in 8 patients (21.6%), and 3) by abnormal physical examination in 9 patients (24.3%). Among these 3 groups, there were statistically significant differences in the intraoperative (p=0.002) and early postoperative neurological deficit (p=0.005) with the lowest deficit in neuronavigation group. However, there were no differences in neurological outcome at later follow up (3-months p=0.103; 6-months p=0.285). There were no differences in the degree of resection among the groups. Continuous physical examination has shown to be of value as an additional layer of monitoring of subcortical white matter during resection and combining several methods may help increase the efficacy of mapping and monitoring of subcortical functions. Copyright © 2016 Elsevier B.V. All rights reserved.

Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment.

PubMed

Canuet, Leonides; Pusil, Sandra; López, María Eugenia; Bajo, Ricardo; Pineda-Pardo, José Ángel; Cuesta, Pablo; Gálvez, Gerardo; Gaztelu, José María; Lourido, Daniel; García-Ribas, Guillermo; Maestú, Fernando

2015-07-15

Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. Resting-state magnetoencephalography (MEG) was used to assess whether functional connectivity patterns, as an index of synaptic dysfunction, are associated with CSF biomarkers [i.e., phospho-tau (p-tau) and amyloid beta (Aβ42) levels]. We studied 12 human subjects diagnosed with mild cognitive impairment due to Alzheimer's disease, comparing those with normal and abnormal CSF levels of the biomarkers. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One-third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF p-tau and Aβ42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by p-tau was associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the default mode network and the temporal cortex. MEG is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization. In this preliminary study, we used magnetoencephalography and an integrative approach to explore the impact of CSF biomarkers, neuropsychological scores, and white matter structural abnormalities on neural function in mild cognitive impairment. Disruption in functional connectivity between several pairs of cortical regions associated with abnormal levels of biomarkers, cognitive deficits, or with impaired axonal integrity of hippocampal tracts. Amyloid deposition and tau protein-related neuronal injury in early Alzheimer's disease are associated with synaptic dysfunction and a dual pattern of cortical network disorganization (i.e., desynchronization and hypersynchronization) that affects key regions of the default mode network and temporal areas. Copyright © 2015 the authors 0270-6474/15/3510326-06$15.00/0.

Minimum spanning tree analysis of the human connectome.

PubMed

van Dellen, Edwin; Sommer, Iris E; Bohlken, Marc M; Tewarie, Prejaas; Draaisma, Laurijn; Zalesky, Andrew; Di Biase, Maria; Brown, Jesse A; Douw, Linda; Otte, Willem M; Mandl, René C W; Stam, Cornelis J

2018-06-01

One of the challenges of brain network analysis is to directly compare network organization between subjects, irrespective of the number or strength of connections. In this study, we used minimum spanning tree (MST; a unique, acyclic subnetwork with a fixed number of connections) analysis to characterize the human brain network to create an empirical reference network. Such a reference network could be used as a null model of connections that form the backbone structure of the human brain. We analyzed the MST in three diffusion-weighted imaging datasets of healthy adults. The MST of the group mean connectivity matrix was used as the empirical null-model. The MST of individual subjects matched this reference MST for a mean 58%-88% of connections, depending on the analysis pipeline. Hub nodes in the MST matched with previously reported locations of hub regions, including the so-called rich club nodes (a subset of high-degree, highly interconnected nodes). Although most brain network studies have focused primarily on cortical connections, cortical-subcortical connections were consistently present in the MST across subjects. Brain network efficiency was higher when these connections were included in the analysis, suggesting that these tracts may be utilized as the major neural communication routes. Finally, we confirmed that MST characteristics index the effects of brain aging. We conclude that the MST provides an elegant and straightforward approach to analyze structural brain networks, and to test network topological features of individual subjects in comparison to empirical null models. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Interpersonal relationship quality mediates the association between military-related posttraumatic stress and academic dysfunction among student veterans.

PubMed

Fredman, Steffany J; Marshall, Amy D; Le, Yunying; Aronson, Keith R; Perkins, Daniel F; Hayes, Jeffrey A

2018-05-03

Large numbers of United States service members and veterans are enrolling in colleges and universities. Many are experiencing posttraumatic stress symptoms secondary to their military service, and these symptoms are associated with academic dysfunction. However, little is known about the mechanism(s) through which posttraumatic stress increases risk for academic difficulties. The goal of the current study was to evaluate perceived interpersonal relationship quality as a mediator of this association. The current study investigated the indirect effect of posttraumatic stress on academic dysfunction through three indices of perceived interpersonal relationship quality (i.e., family distress, family support, and social network support) in a clinical sample of 2,120 student service members and veterans. Participants were further divided into four groups based on relationship status and gender (i.e., partnered women, nonpartnered women, partnered men, and nonpartnered men), and moderation by group was examined. For all four groups, there were significant indirect effects of posttraumatic stress on academic dysfunction through greater family distress and lower social network support. Further, the overall indirect effect of posttraumatic stress on academic dysfunction was stronger for partnered women compared with the three other groups and was attributable to the stronger path from family distress to academic dysfunction for partnered women. Poor perceived relationship quality may be a modifiable risk factor for academic dysfunction among student service members and veterans experiencing military-related posttraumatic stress. Partnered women may be especially well-suited to interventions that enhance the interpersonal context of posttraumatic stress as a way to optimize academic outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Subcortical Band Heterotopia (SBH) in Rat Offspring Following Maternal Hypothyroxinemia: Structural and Functional Characteristics

EPA Science Inventory

Thyroid hormones (TH) play crucial roles in brain maturation, neuronal migration, and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported...

Imaging Effects of Neurotrophic Factor Genes on Brain Plasticity and Repair in Multiple Sclerosis

DTIC Science & Technology

2010-07-01

cortical thickness and subcortical volume measures, lesion volumetry , and voxel-based morphometry and diffusion imaging. We are continuing to...th ickness and subcortical volume measures, lesion volumetry , and voxel-based morphometry and diffusion imaging. Regressio n and symbolic modeling

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex.

PubMed

Guadalupe, Tulio; Mathias, Samuel R; vanErp, Theo G M; Whelan, Christopher D; Zwiers, Marcel P; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A; Arias-Vásquez, Alejandro; Aribisala, Benjamin S; Armstrong, Nicola J; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E; Baune, Bernhard T; Blangero, John; Bokde, Arun L W; Boedhoe, Premika S W; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Büchel, Christian; Buitelaar, Jan; Calhoun, Vince D; Cannon, Dara M; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; de Zubicaray, Greig I; de Zwarte, Sonja M C; Deary, Ian J; Desrivières, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dørum, Erlend S; Ehrlich, Stefan; Espeseth, Thomas; Fernández, Guillén; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jürgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U; Heinz, Andreas; Hibar, Derrek P; Hoekstra, Pieter J; Hoogman, Martine; Howells, Fleur M; Hu, Hao; Hulshoff Pol, Hilleke E; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jönsson, Erik G; Jurk, Sarah; Kahn, Rene S; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F; Martin, Nicholas G; Martínez-Zalacaín, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L; Medland, Sarah E; Menchón, José M; Morris, Derek W; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C; Nees, Frauke; Nordvik, Jan E; Onnink, A Marten H; Opel, Nils; Ophoff, Roel; Paillère Martinot, Marie-Laure; Papadopoulos Orfanos, Dimitri; Pauli, Paul; Paus, Tomáš; Poustka, Luise; Reddy, Janardhan Yc; Renteria, Miguel E; Roiz-Santiáñez, Roberto; Roos, Annerine; Royle, Natalie A; Sachdev, Perminder; Sánchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N; Soares, Jair C; Soriano-Mas, Carles; Stein, Dan J; Strike, Lachlan T; Toro, Roberto; Turner, Jessica A; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernández, Maria Valdés; van den Heuvel, Odile A; van der Meer, Dennis; van Haren, Neeltje E M; Veltman, Dick J; Venkatasubramanian, Ganesan; Vetter, Nora C; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M; Glahn, David C; Mazoyer, Bernard; Fisher, Simon E; Francks, Clyde

2017-10-01

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei

PubMed Central

Pauli, Wolfgang M.; Nili, Amanda N.; Tyszka, J. Michael

2018-01-01

Recent advances in magnetic resonance imaging methods, including data acquisition, pre-processing and analysis, have benefited research on the contributions of subcortical brain nuclei to human cognition and behavior. At the same time, these developments have led to an increasing need for a high-resolution probabilistic in vivo anatomical atlas of subcortical nuclei. In order to address this need, we constructed high spatial resolution, three-dimensional templates, using high-accuracy diffeomorphic registration of T1- and T2- weighted structural images from 168 typical adults between 22 and 35 years old. In these templates, many tissue boundaries are clearly visible, which would otherwise be impossible to delineate in data from individual studies. The resulting delineations of subcortical nuclei complement current histology-based atlases. We further created a companion library of software tools for atlas development, to offer an open and evolving resource for the creation of a crowd-sourced in vivo probabilistic anatomical atlas of the human brain. PMID:29664465

Shared rhythmic subcortical GABAergic input to the entorhinal cortex and presubiculum

PubMed Central

Salib, Minas; Joshi, Abhilasha; Unal, Gunes; Berry, Naomi

2018-01-01

Rhythmic theta frequency (~5–12 Hz) oscillations coordinate neuronal synchrony and higher frequency oscillations across the cortex. Spatial navigation and context-dependent episodic memories are represented in several interconnected regions including the hippocampal and entorhinal cortices, but the cellular mechanisms for their dynamic coupling remain to be defined. Using monosynaptically-restricted retrograde viral tracing in mice, we identified a subcortical GABAergic input from the medial septum that terminated in the entorhinal cortex, with collaterals innervating the dorsal presubiculum. Extracellularly recording and labeling GABAergic entorhinal-projecting neurons in awake behaving mice show that these subcortical neurons, named orchid cells, fire in long rhythmic bursts during immobility and locomotion. Orchid cells discharge near the peak of hippocampal and entorhinal theta oscillations, couple to entorhinal gamma oscillations, and target subpopulations of extra-hippocampal GABAergic interneurons. Thus, orchid cells are a specialized source of rhythmic subcortical GABAergic modulation of ‘upstream’ and ‘downstream’ cortico-cortical circuits involved in mnemonic functions. PMID:29620525

Shared rhythmic subcortical GABAergic input to the entorhinal cortex and presubiculum.

PubMed

Viney, Tim James; Salib, Minas; Joshi, Abhilasha; Unal, Gunes; Berry, Naomi; Somogyi, Peter

2018-04-05

Rhythmic theta frequency (~5-12 Hz) oscillations coordinate neuronal synchrony and higher frequency oscillations across the cortex. Spatial navigation and context-dependent episodic memories are represented in several interconnected regions including the hippocampal and entorhinal cortices, but the cellular mechanisms for their dynamic coupling remain to be defined. Using monosynaptically-restricted retrograde viral tracing in mice, we identified a subcortical GABAergic input from the medial septum that terminated in the entorhinal cortex, with collaterals innervating the dorsal presubiculum. Extracellularly recording and labeling GABAergic entorhinal-projecting neurons in awake behaving mice show that these subcortical neurons, named orchid cells, fire in long rhythmic bursts during immobility and locomotion. Orchid cells discharge near the peak of hippocampal and entorhinal theta oscillations, couple to entorhinal gamma oscillations, and target subpopulations of extra-hippocampal GABAergic interneurons. Thus, orchid cells are a specialized source of rhythmic subcortical GABAergic modulation of 'upstream' and 'downstream' cortico-cortical circuits involved in mnemonic functions. © 2018, Viney et al.

Disrupted Small-World Networks in Schizophrenia

ERIC Educational Resources Information Center

Liu, Yong; Liang, Meng; Zhou, Yuan; He, Yong; Hao, Yihui; Song, Ming; Yu, Chunshui; Liu, Haihong; Liu, Zhening; Jiang, Tianzi

2008-01-01

The human brain has been described as a large, sparse, complex network characterized by efficient small-world properties, which assure that the brain generates and integrates information with high efficiency. Many previous neuroimaging studies have provided consistent evidence of "dysfunctional connectivity" among the brain regions in…

Changes in neural network homeostasis trigger neuropsychiatric symptoms.

PubMed

Winkelmann, Aline; Maggio, Nicola; Eller, Joanna; Caliskan, Gürsel; Semtner, Marcus; Häussler, Ute; Jüttner, René; Dugladze, Tamar; Smolinsky, Birthe; Kowalczyk, Sarah; Chronowska, Ewa; Schwarz, Günter; Rathjen, Fritz G; Rechavi, Gideon; Haas, Carola A; Kulik, Akos; Gloveli, Tengis; Heinemann, Uwe; Meier, Jochen C

2014-02-01

The mechanisms that regulate the strength of synaptic transmission and intrinsic neuronal excitability are well characterized; however, the mechanisms that promote disease-causing neural network dysfunction are poorly defined. We generated mice with targeted neuron type-specific expression of a gain-of-function variant of the neurotransmitter receptor for glycine (GlyR) that is found in hippocampectomies from patients with temporal lobe epilepsy. In this mouse model, targeted expression of gain-of-function GlyR in terminals of glutamatergic cells or in parvalbumin-positive interneurons persistently altered neural network excitability. The increased network excitability associated with gain-of-function GlyR expression in glutamatergic neurons resulted in recurrent epileptiform discharge, which provoked cognitive dysfunction and memory deficits without affecting bidirectional synaptic plasticity. In contrast, decreased network excitability due to gain-of-function GlyR expression in parvalbumin-positive interneurons resulted in an anxiety phenotype, but did not affect cognitive performance or discriminative associative memory. Our animal model unveils neuron type-specific effects on cognition, formation of discriminative associative memory, and emotional behavior in vivo. Furthermore, our data identify a presynaptic disease-causing molecular mechanism that impairs homeostatic regulation of neural network excitability and triggers neuropsychiatric symptoms.

Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: a retrospective cohort study in The Health Improvement Network

PubMed Central

Rowan, Christopher G.; Brunelli, Steven M.; Munson, Jeffrey; Flory, James; Reese, Peter P.; Hennessy, Sean; Lewis, James; Mines, Daniel; Barrett, Jeffrey S.; Bilker, Warren; Strom, Brian L.

2014-01-01

Objective To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme. Background Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism. Methods Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score. Results The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362 809 patients and 792 665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90–1.66). There were 1449 renal dysfunction events among 272,099 patients and 574 584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58–1.44). There were 1434 hepatic dysfunction events among 367 612 patients and 815 945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45–1.31). Conclusions Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy. PMID:22422642

Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction in Schizophrenia.

PubMed

Avery, Suzanne N; Rogers, Baxter P; Heckers, Stephan

2018-05-01

Functional dysconnectivity has been proposed as a major pathophysiological mechanism for cognitive dysfunction in schizophrenia. The hippocampus is a focal point of dysconnectivity in schizophrenia, with decreased hippocampal functional connectivity contributing to the marked memory deficits observed in patients. Normal memory function relies on the interaction of complex corticohippocampal networks. However, only recent technological advances have enabled the large-scale exploration of functional networks with accuracy and precision. We investigated the modularity of hippocampal resting-state functional networks in a sample of 45 patients with schizophrenia spectrum disorders and 38 healthy control subjects. Modularity was calculated for two distinct functional networks: a core hippocampal-medial temporal lobe cortex network and an extended hippocampal-cortical network. As hippocampal function differs along its longitudinal axis, follow-up analyses examined anterior and posterior networks separately. To explore effects of resting network function on behavior, we tested associations between modularity and relational memory ability. Age, sex, handedness, and parental education were similar between groups. Network modularity was lower in schizophrenia patients, especially in the posterior hippocampal network. Schizophrenia patients also showed markedly lower relational memory ability compared with control subjects. We found a distinct brain-behavior relationship in schizophrenia that differed from control subjects by network and anterior/posterior division-while relational memory in control subjects was associated with anterior hippocampal-cortical modularity, schizophrenia patients showed an association with posterior hippocampal-medial temporal lobe cortex network modularity. Our findings support a model of abnormal resting-state corticohippocampal network coherence in schizophrenia, which may contribute to relational memory deficits. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Towards systems neuroscience of ADHD: A meta-analysis of 55 fMRI studies

PubMed Central

Cortese, Samuele; Kelly, Clare; Chabernaud, Camille; Proal, Erika; Di Martino, Adriana; Milham, Michael P.; Castellanos, F. Xavier

2013-01-01

Objective To perform a comprehensive meta-analysis of task-based functional MRI studies of Attention-Deficit/Hyperactivity Disorder (ADHD). Method PubMed, Ovid, EMBASE, Web of Science, ERIC, CINHAL, and NeuroSynth were searched for studies published through 06/30/2011. Significant differences in activation of brain regions between individuals with ADHD and comparisons were detected using activation likelihood estimation meta-analysis (p<0.05, corrected). Dysfunctional regions in ADHD were related to seven reference neuronal systems. We performed a set of meta-analyses focused on age groups (children; adults), clinical characteristics (history of stimulant treatment; presence of psychiatric comorbidities), and specific neuropsychological tasks (inhibition; working memory; vigilance/attention). Results Fifty-five studies were included (39 in children, 16 in adults). In children, hypoactivation in ADHD vs. comparisons was found mostly in systems involved in executive functions (frontoparietal network) and attention (ventral attentional network). Significant hyperactivation in ADHD vs. comparisons was observed predominantly within the default, ventral attention, and somatomotor networks. In adults, ADHD-related hypoactivation was predominant in the frontoparietal system, while ADHD-related hyperactivation was present in the visual, dorsal attention, and default networks. Significant ADHD-related dysfunction largely reflected task features and was detected even in the absence of comorbid mental disorders or history of stimulant treatment. Conclusions A growing literature provides evidence of ADHD-related dysfunction within multiple neuronal systems involved in higher-level cognitive functions but also in sensorimotor processes, including the visual system, and in the default network. This meta-analytic evidence extends early models of ADHD pathophysiology focused on prefrontal-striatal circuits. PMID:22983386

Early grey matter changes in structural covariance networks in Huntington's disease.

PubMed

Coppen, Emma M; van der Grond, Jeroen; Hafkemeijer, Anne; Rombouts, Serge A R B; Roos, Raymund A C

2016-01-01

Progressive subcortical changes are known to occur in Huntington's disease (HD), a hereditary neurodegenerative disorder. Less is known about the occurrence and cohesion of whole brain grey matter changes in HD. We aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments. Structural magnetic resonance imaging data of premanifest HD ( n  = 30), HD patients (n = 30) and controls (n = 30) was used to identify ten structural covariance networks based on a novel technique using the co-variation of grey matter with independent component analysis in FSL. Group differences were studied controlling for age and gender. To explore whether our approach is effective in examining grey matter changes, regional voxel-based analysis was additionally performed. Premanifest HD and HD patients showed decreased network integrity in two networks compared to controls. One network included the caudate nucleus, precuneous and anterior cingulate cortex (in HD p  < 0.001, in pre-HD p  = 0.003). One other network contained the hippocampus, premotor, sensorimotor, and insular cortices (in HD p  < 0.001, in pre-HD p  = 0.023). Additionally, in HD patients only, decreased network integrity was observed in a network including the lingual gyrus, intracalcarine, cuneal, and lateral occipital cortices ( p  = 0.032). Changes in network integrity were significantly associated with scores of motor and neuropsychological assessments. In premanifest HD, voxel-based analyses showed pronounced volume loss in the basal ganglia, but less prominent in cortical regions. Our results suggest that structural covariance might be a sensitive approach to reveal early grey matter changes, especially for premanifest HD.

Neuroradiologic correlation with aphasias. Cortico-subcortical map of language.

PubMed

Jiménez de la Peña, M M; Gómez Vicente, L; García Cobos, R; Martínez de Vega, V

Aphasia is an acquired language disorder due to a cerebral lesion; it is characterized by errors in production, denomination, or comprehension of language. Although most aphasias are mixed, from a practical point of view they are classified into different types according to their main clinical features: Broca's aphasia, Wernicke's aphasia, conduction aphasia, transcortical aphasia, and alexia with or without agraphia. We present the clinical findings for the main subtypes of aphasia, illustrating them with imaging cases, and we provide an up-to-date review of the language network with images from functional magnetic resonance imaging and tractography. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Pain perception and hypnosis: findings from recent functional neuroimaging studies.

PubMed

Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; Serata, Daniele; Caltagirone, Saverio Simone; Savoja, Valeria; Piacentino, Daria; Callovini, Gemma; Manfredi, Giovanni; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

2015-01-01

Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimaging studies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimaging studies support the clinical use of hypnosis in the management of pain conditions.

Improved naming after TMS treatments in a chronic, global aphasia patient — case report

PubMed Central

NAESER, MARGARET A.; MARTIN, PAULA I; NICHOLAS, MARJORIE; BAKER, ERROL H.; SEEKINS, HEIDI; HELM-ESTABROOKS, NANCY; CAYER-MEADE, CAROL; KOBAYASHI, MASAHITO; THEORET, HUGO; FREGNI, FELIPE; TORMOS, JOSE MARIA; KURLAND, JACQUIE; DORON, KARL W.; PASCUAL-LEONE, ALVARO

2005-01-01

We report improved ability to name pictures at 2 and 8 months after repetitive transcranial magnetic stimulation (rTMS) treatments to the pars triangularis portion of right Broca’s homologue in a 57 year-old woman with severe nonfluent/global aphasia (6.5 years post left basal ganglia bleed, subcortical lesion). TMS was applied at 1 Hz, 20 minutes a day, 10 days, over a two-week period. She received no speech therapy during the study. One year after her TMS treatments, she entered speech therapy with continued improvement. TMS may have modulated activity in the remaining left and right hemisphere neural network for naming. PMID:16006338

Proverb interpretation changes in aging.

PubMed

Uekermann, Jennifer; Thoma, Patrizia; Daum, Irene

2008-06-01

Recent investigations have emphasized the involvement of fronto-subcortical networks to proverb comprehension. Although the prefrontal cortex is thought to be affected by normal aging, relatively little work has been carried out to investigate potential effects of aging on proverb comprehension. In the present investigation participants in three age groups were assessed on a proverb comprehension task and a range of executive function tasks. The older group showed impairment in selecting correct interpretations from alternatives. They also showed executive function deficits, as reflected by reduced working memory and deficient set shifting and inhibition abilities. The findings of the present investigation showed proverb comprehension deficits in normal aging which appeared to be related to reduced executive skills.

Friedrich Nietzsche and his illness: a neurophilosophical approach to introspection.

PubMed

Perogamvros, Lampros; Perrig, Stephen; Bogousslavsky, Julien; Giannakopoulos, Panteleimon

2013-01-01

There are some arguments that Friedrich Nietzsche suffered from the autosomal dominant vascular microangiopathy: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Here, a hypothesis is formulated supporting that CADASIL presenting with symptoms of bipolar disorder and Gastaut-Geschwind syndrome would contribute to the increased insight and creativity of a philosopher whose perceptions and intuitions often bear out the results of modern neuroscience. Alterations of the brain default and reward networks would account for such an increased level of introspection and creativity. A new framework on approaching illness is proposed, which, in conformity with Nietzsche's positive view, outlines the enabling aspects of some otherwise highly disabling neuropsychiatric disorders.

Decoding the Nature of Emotion in the Brain.

PubMed

Kragel, Philip A; LaBar, Kevin S

2016-06-01

A central, unresolved problem in affective neuroscience is understanding how emotions are represented in nervous system activity. After prior localization approaches largely failed, researchers began applying multivariate statistical tools to reconceptualize how emotion constructs might be embedded in large-scale brain networks. Findings from pattern analyses of neuroimaging data show that affective dimensions and emotion categories are uniquely represented in the activity of distributed neural systems that span cortical and subcortical regions. Results from multiple-category decoding studies are incompatible with theories postulating that specific emotions emerge from the neural coding of valence and arousal. This 'new look' into emotion representation promises to improve and reformulate neurobiological models of affect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decoding the Nature of Emotion in the Brain

PubMed Central

Kragel, Philip A.; LaBar, Kevin S.

2016-01-01

A central, unresolved problem in affective neuroscience is understanding how emotions are represented in nervous system activity. After prior localization approaches largely failed, researchers began applying multivariate statistical tools to reconceptualize how emotion constructs might be embedded in large-scale brain networks. Findings from pattern analyses of neuroimaging data show that affective dimensions and emotion categories are uniquely represented in the activity of distributed neural systems that span cortical and subcortical regions. Results from multiple-category decoding studies are incompatible with theories postulating that specific emotions emerge from the neural coding of valence and arousal. This ‘new look’ into emotion representation promises to improve and reformulate neurobiological models of affect. PMID:27133227

Imaging Effects of Neurotrophic Factor Genes on Brain Plasticity and Repair in Multiple Sclerosis

DTIC Science & Technology

2011-07-01

focal and diffuse effects in brain (including cortical thickness and subcortical volume measures, lesion volumetry , and voxel-based morphometry and...to both focal and diffuse effects in gray and white matter, including cortical thickness and subcortical volume measures, lesion volumetry , and

The Development of Human Amygdala Functional Connectivity at Rest from 4 to 23 Years: a cross-sectional study

PubMed Central

Gabard-Durnam, Laurel J.; Flannery, Jessica; Goff, Bonnie; Gee, Dylan G.; Humphreys, Kathryn L.; Telzer, Eva; Hare, Todd; Tottenham, Nim

2014-01-01

Functional connections (FC) between the amygdala and cortical and subcortical regions underlie a range of affective and cognitive processes. Despite the central role amygdala networks have in these functions, the normative developmental emergence of FC between the amygdala and the rest of the brain is still largely undefined. This study employed amygdala subregion maps and resting-state functional magnetic resonance imaging to characterize the typical development of human amygdala FC from age 4 to 23 years old (n = 58). Amygdala FC with subcortical and limbic regions was largely stable across this developmental period. However, three cortical regions exhibited age-dependent changes in FC: amygdala FC with the medial prefrontal cortex (mPFC) increased with age, while amygdala FC with a region including the insula and superior temporal sulcus decreased with age, and amygdala FC with a region encompassing the parahippocampal gyrus and posterior cingulate also decreased with age. The transition from childhood to adolescence (around age 10 years) marked an important change-point in the nature of amygdala-cortical FC. We distinguished unique developmental patterns of coupling for three amygdala subregions and found particularly robust convergence of FC for all subregions with the mPFC. These findings suggest that there are extensive changes in amygdala-cortical functional connectivity that emerge between childhood and adolescence. PMID:24662579

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.

PubMed

Barrio, Jorge R; Small, Gary W; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A; Giza, Christopher C; Fitzsimmons, Robert P; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

2015-04-21

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.

Frontal Transcranial Direct Current Stimulation Induces Dopamine Release in the Ventral Striatum in Human

PubMed Central

Fonteneau, Clara; Redoute, Jérome; Haesebaert, Frédéric; Le Bars, Didier; Costes, Nicolas; Suaud-Chagny, Marie-Françoise; Brunelin, Jérome

2018-01-01

Abstract A single transcranial direct current stimulation (tDCS) session applied over the dorsolateral prefrontal cortex (DLFPC) can be associated with procognitive effects. Furthermore, repeated DLPFC tDCS sessions are under investigation as a new therapeutic tool for a range of neuropsychiatric conditions. A possible mechanism explaining such beneficial effects is a modulation of meso-cortico-limbic dopamine transmission. We explored the spatial and temporal neurobiological effects of bifrontal tDCS on subcortical dopamine transmission during and immediately after the stimulation. In a double blind sham-controlled study, 32 healthy subjects randomly received a single session of either active (20 min, 2 mA; n = 14) or sham (n = 18) tDCS during a dynamic positron emission tomography scan using [11C]raclopride binding. During the stimulation period, no significant effect of tDCS was observed. After the stimulation period, compared with sham tDCS, active tDCS induced a significant decrease in [11C]raclopride binding potential ratio in the striatum, suggesting an increase in extracellular dopamine in a part of the striatum involved in the reward–motivation network. The present study provides the first evidence that bifrontal tDCS induces neurotransmitter release in polysynaptic connected subcortical areas. Therefore, levels of dopamine activity and reactivity should be a new element to consider for a general hypothesis of brain modulation by bifrontal tDCS. PMID:29688276

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging

PubMed Central

Barrio, Jorge R.; Small, Gary W.; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A.; Giza, Christopher C.; Fitzsimmons, Robert P.; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

2015-01-01

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer’s dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE. PMID:25848027

Frontal Transcranial Direct Current Stimulation Induces Dopamine Release in the Ventral Striatum in Human.

PubMed

Fonteneau, Clara; Redoute, Jérome; Haesebaert, Frédéric; Le Bars, Didier; Costes, Nicolas; Suaud-Chagny, Marie-Françoise; Brunelin, Jérome

2018-07-01

A single transcranial direct current stimulation (tDCS) session applied over the dorsolateral prefrontal cortex (DLFPC) can be associated with procognitive effects. Furthermore, repeated DLPFC tDCS sessions are under investigation as a new therapeutic tool for a range of neuropsychiatric conditions. A possible mechanism explaining such beneficial effects is a modulation of meso-cortico-limbic dopamine transmission. We explored the spatial and temporal neurobiological effects of bifrontal tDCS on subcortical dopamine transmission during and immediately after the stimulation. In a double blind sham-controlled study, 32 healthy subjects randomly received a single session of either active (20 min, 2 mA; n = 14) or sham (n = 18) tDCS during a dynamic positron emission tomography scan using [11C]raclopride binding. During the stimulation period, no significant effect of tDCS was observed. After the stimulation period, compared with sham tDCS, active tDCS induced a significant decrease in [11C]raclopride binding potential ratio in the striatum, suggesting an increase in extracellular dopamine in a part of the striatum involved in the reward-motivation network. The present study provides the first evidence that bifrontal tDCS induces neurotransmitter release in polysynaptic connected subcortical areas. Therefore, levels of dopamine activity and reactivity should be a new element to consider for a general hypothesis of brain modulation by bifrontal tDCS.

Segregated fronto‐cortical and midbrain connections in the mouse and their relation to approach and avoidance orienting behaviors

PubMed Central

Savage, Michael Anthony; McQuade, Richard

2017-01-01

Abstract The orchestration of orienting behaviors requires the interaction of many cortical and subcortical areas, for example the superior colliculus (SC), as well as prefrontal areas responsible for top–down control. Orienting involves different behaviors, such as approach and avoidance. In the rat, these behaviors are at least partially mapped onto different SC subdomains, the lateral (SCl) and medial (SCm), respectively. To delineate the circuitry involved in the two types of orienting behavior in mice, we injected retrograde tracer into the intermediate and deep layers of the SCm and SCl, and thereby determined the main input structures to these subdomains. Overall the SCm receives larger numbers of afferents compared to the SCl. The prefrontal cingulate area (Cg), visual, oculomotor, and auditory areas provide strong input to the SCm, while prefrontal motor area 2 (M2), and somatosensory areas provide strong input to the SCl. The prefrontal areas Cg and M2 in turn connect to different cortical and subcortical areas, as determined by anterograde tract tracing. Even though connectivity pattern often overlap, our labeling approaches identified segregated neural circuits involving SCm, Cg, secondary visual cortices, auditory areas, and the dysgranular retrospenial cortex likely to be involved in avoidance behaviors. Conversely, SCl, M2, somatosensory cortex, and the granular retrospenial cortex comprise a network likely involved in approach/appetitive behaviors. PMID:28177526

Dysphagia Post Subcortical and Supratentorial Stroke.

PubMed

Wan, Ping; Chen, Xuhui; Zhu, Lequn; Xu, Shuangjin; Huang, Li; Li, Xiangcui; Ye, Qing; Ding, Ruiying

2016-01-01

Studies have recognized that the damage in the subcortical and supratentorial regions may affect voluntary and involuntary aspects of the swallowing function. The current study attempted to explore the dysphagia characteristics in patients with subcortical and supratentorial stroke. Twelve post first or second subcortical and supratentorial stroke patients were included in the study. The location of the stroke was ascertained by computed tomography and magnetic resonance imaging. The characteristics of swallowing disorder were assessed by video fluoroscopic swallowing assessment/fiberoptic endoscopic evaluation of swallowing. The following main parameters were analyzed: oral transit time, pharyngeal delay time, presence of cricopharyngeal muscle achalasia (CMA), distance of laryngeal elevation, the amounts of vallecular residue and pyriform sinus residue (PSR), and the extent of pharyngeal contraction. Eighty-three percent of the 12 patients were found suffering from pharyngeal dysphagia, with 50% having 50%-100% PSRs, 50% having pharyngeal delay, and 41.6% cases demonstrating CMA. Simple regression analysis showed PSRs were most strongly associated with CMA. Pharyngeal delay in the study can be caused by infarcts of basal ganglia/thalamus, infarcts of sensory tract, infarcts of swallowing motor pathways in the centrum semiovale, or a combination of the three. Subcortical and supratentorial stroke may result in pharyngeal dysphagia such as PSR and pharyngeal delay. PSR was mainly caused by CMA. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

NASA Astrophysics Data System (ADS)

Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

2015-11-01

Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

Phonemic Characteristics of Apraxia of Speech Resulting from Subcortical Hemorrhage

ERIC Educational Resources Information Center

Peach, Richard K.; Tonkovich, John D.

2004-01-01

Reports describing subcortical apraxia of speech (AOS) have received little consideration in the development of recent speech processing models because the speech characteristics of patients with this diagnosis have not been described precisely. We describe a case of AOS with aphasia secondary to basal ganglia hemorrhage. Speech-language symptoms…

Gross Brain Morphology in Schizophrenia: A Regional Analysis of Traditional Diagnostic Subtypes.

ERIC Educational Resources Information Center

Raz, Sarah

1994-01-01

Categorized 56 patients with chronic schizophrenia into 2 groups based on traditional diagnostic subtypology. Compared groups on indices of cortical and subcortical cerebrospinal fluid (SCF) volume to explore whether more virulent nonparanoid disorder was linked to cortical/subcortical morphological brain abnormalities. Two groups differed…

The Differential Effects of Thalamus and Basal Ganglia on Facial Emotion Recognition

ERIC Educational Resources Information Center

Cheung, Crystal C. Y.; Lee, Tatia M. C.; Yip, James T. H.; King, Kristin E.; Li, Leonard S. W.

2006-01-01

This study examined if subcortical stroke was associated with impaired facial emotion recognition. Furthermore, the lateralization of the impairment and the differential profiles of facial emotion recognition deficits with localized thalamic or basal ganglia damage were also studied. Thirty-eight patients with subcortical strokes and 19 matched…

Imaging Effects of Neurotrophic Factor Genes on Brain Plasticity and Repair in Multiple Sclerosis

DTIC Science & Technology

2012-07-01

sensitive to focal and diffuse changes in brain tissue (including cortical thickness and subcortical volume measures, lesion volumetry , and voxel-based...sensitive to both focal and diffuse effects in gray and white matter, including cortical thickness and subcortical volume measures, lesion volumetry , and

Multimodal neuroimaging investigations of alterations to consciousness: the relationship between absence epilepsy and sleep.

PubMed

Bagshaw, Andrew P; Rollings, David T; Khalsa, Sakh; Cavanna, Andrea E

2014-01-01

The link between epilepsy and sleep is well established on many levels. The focus of the current review is on recent neuroimaging investigations into the alterations of consciousness that are observed during absence seizures and the descent into sleep. Functional neuroimaging provides simultaneous cortical and subcortical recording of activity throughout the brain, allowing a detailed definition and characterization of large-scale brain networks and the interactions between them. This has led to the identification of a set of regions which collectively form the consciousness system, which includes contributions from the default mode network (DMN), ascending arousal systems, and the thalamus. Electrophysiological and neuroimaging investigations have also clearly demonstrated the importance of thalamocortical and corticothalamic networks in the evolution of sleep and absence epilepsy, two phenomena in which the subject experiences an alteration to the conscious state and a disconnection from external input. However, the precise relationship between the consciousness system, thalamocortical networks, and consciousness itself remains to be clarified. One of the fundamental challenges is to understand how distributed brain networks coordinate their activity in order to maintain and implement complex behaviors such as consciousness and how modifications to this network activity lead to alterations in consciousness. By taking into account not only the level of activation of individual brain regions but also their connectivity within specific networks and the activity and connectivity of other relevant networks, a more specific quantification of brain states can be achieved. This, in turn, may provide a more fundamental understanding of the alterations to consciousness experienced in sleep and epilepsy. © 2013.

Detecting brain dynamics during resting state: a tensor based evolutionary clustering approach

NASA Astrophysics Data System (ADS)

Al-sharoa, Esraa; Al-khassaweneh, Mahmood; Aviyente, Selin

2017-08-01

Human brain is a complex network with connections across different regions. Understanding the functional connectivity (FC) of the brain is important both during resting state and task; as disruptions in connectivity patterns are indicators of different psychopathological and neurological diseases. In this work, we study the resting state functional connectivity networks (FCNs) of the brain from fMRI BOLD signals. Recent studies have shown that FCNs are dynamic even during resting state and understanding the temporal dynamics of FCNs is important for differentiating between different conditions. Therefore, it is important to develop algorithms to track the dynamic formation and dissociation of FCNs of the brain during resting state. In this paper, we propose a two step tensor based community detection algorithm to identify and track the brain network community structure across time. First, we introduce an information-theoretic function to reduce the dynamic FCN and identify the time points that are similar topologically to combine them into a tensor. These time points will be used to identify the different FC states. Second, a tensor based spectral clustering approach is developed to identify the community structure of the constructed tensors. The proposed algorithm applies Tucker decomposition to the constructed tensors and extract the orthogonal factor matrices along the connectivity mode to determine the common subspace within each FC state. The detected community structure is summarized and described as FC states. The results illustrate the dynamic structure of resting state networks (RSNs), including the default mode network, somatomotor network, subcortical network and visual network.

The hearing ear is always found close to the speaking tongue: Review of the role of the motor system in speech perception.

PubMed

Skipper, Jeremy I; Devlin, Joseph T; Lametti, Daniel R

2017-01-01

Does "the motor system" play "a role" in speech perception? If so, where, how, and when? We conducted a systematic review that addresses these questions using both qualitative and quantitative methods. The qualitative review of behavioural, computational modelling, non-human animal, brain damage/disorder, electrical stimulation/recording, and neuroimaging research suggests that distributed brain regions involved in producing speech play specific, dynamic, and contextually determined roles in speech perception. The quantitative review employed region and network based neuroimaging meta-analyses and a novel text mining method to describe relative contributions of nodes in distributed brain networks. Supporting the qualitative review, results show a specific functional correspondence between regions involved in non-linguistic movement of the articulators, covertly and overtly producing speech, and the perception of both nonword and word sounds. This distributed set of cortical and subcortical speech production regions are ubiquitously active and form multiple networks whose topologies dynamically change with listening context. Results are inconsistent with motor and acoustic only models of speech perception and classical and contemporary dual-stream models of the organization of language and the brain. Instead, results are more consistent with complex network models in which multiple speech production related networks and subnetworks dynamically self-organize to constrain interpretation of indeterminant acoustic patterns as listening context requires. Copyright © 2016. Published by Elsevier Inc.

The Amygdala: An Agent of Change in Adolescent Neural Networks

PubMed Central

Scherf, K. Suzanne; Smyth, Joshua M.; Delgado, Mauricio R.

2013-01-01

A unique component of adolescent development is the need to master new developmental tasks in which peer interactions become primary (for the purposes of becoming autonomous from parents, forming intimate friendships, and romantic/sexual partnerships). Previously, it has been suggested that the ability to master these tasks requires an important re-organization in the relation between perceptual, motivational, affective, and cognitive systems in a very general and broad way that is fundamentally influenced by the infusion of sex hormones during pubertal development (Scherf et al., 2012). Herein, we extend this argument to suggest that the amygdala, which is vastly connected with cortical and subcortical regions and contains sex hormone receptors, may lie at the heart of this re-organization. We propose that during adolescent development there is a shift in the attribution of relevance to existing stimuli and contexts that is mediated by the amygdala (e.g., heightened relevance of peer faces, reduced relevance of physical distance from parents). As a result, amygdala inputs to existing stable neural networks are re-weighted (increased or decreased), which destabilizes the functional interactions among regions within these networks and allows for a critical restructuring of the network functional organization. This process of network re-organization enables processing of qualitatively new kinds of social information and the emergence of novel behaviors that support mastery of adolescent-specific developmental tasks. PMID:23756154

Rich-club organization of the newborn human brain

PubMed Central

Ball, Gareth; Aljabar, Paul; Zebari, Sally; Tusor, Nora; Arichi, Tomoki; Merchant, Nazakat; Robinson, Emma C.; Ogundipe, Enitan; Rueckert, Daniel; Edwards, A. David; Counsell, Serena J.

2014-01-01

Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a “rich club”—a high-cost, high-capacity backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical–subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants. PMID:24799693

Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats.

PubMed

Pillay, Siveshigan; Liu, Xiping; Baracskay, Péter; Hudetz, Anthony G

2014-09-01

Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in δ- and θ-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.

Intelligence is associated with the modular structure of intrinsic brain networks.

PubMed

Hilger, Kirsten; Ekman, Matthias; Fiebach, Christian J; Basten, Ulrike

2017-11-22

General intelligence is a psychological construct that captures in a single metric the overall level of behavioural and cognitive performance in an individual. While previous research has attempted to localise intelligence in circumscribed brain regions, more recent work focuses on functional interactions between regions. However, even though brain networks are characterised by substantial modularity, it is unclear whether and how the brain's modular organisation is associated with general intelligence. Modelling subject-specific brain network graphs from functional MRI resting-state data (N = 309), we found that intelligence was not associated with global modularity features (e.g., number or size of modules) or the whole-brain proportions of different node types (e.g., connector hubs or provincial hubs). In contrast, we observed characteristic associations between intelligence and node-specific measures of within- and between-module connectivity, particularly in frontal and parietal brain regions that have previously been linked to intelligence. We propose that the connectivity profile of these regions may shape intelligence-relevant aspects of information processing. Our data demonstrate that not only region-specific differences in brain structure and function, but also the network-topological embedding of fronto-parietal as well as other cortical and subcortical brain regions is related to individual differences in higher cognitive abilities, i.e., intelligence.

The organisation of the elderly connectome.

PubMed

Perry, Alistair; Wen, Wei; Lord, Anton; Thalamuthu, Anbupalam; Roberts, Gloria; Mitchell, Philip B; Sachdev, Perminder S; Breakspear, Michael

2015-07-01

Investigations of the human connectome have elucidated core features of adult structural networks, particularly the crucial role of hub-regions. However, little is known regarding network organisation of the healthy elderly connectome, a crucial prelude to the systematic study of neurodegenerative disorders. Here, whole-brain probabilistic tractography was performed on high-angular diffusion-weighted images acquired from 115 healthy elderly subjects (age 76-94 years; 65 females). Structural networks were reconstructed between 512 cortical and subcortical brain regions. We sought to investigate the architectural features of hub-regions, as well as left-right asymmetries, and sexual dimorphisms. We observed that the topology of hub-regions is consistent with a young adult population, and previously published adult connectomic data. More importantly, the architectural features of hub connections reflect their ongoing vital role in network communication. We also found substantial sexual dimorphisms, with females exhibiting stronger inter-hemispheric connections between cingulate and prefrontal cortices. Lastly, we demonstrate intriguing left-lateralized subnetworks consistent with the neural circuitry specialised for language and executive functions, whilst rightward subnetworks were dominant in visual and visuospatial streams. These findings provide insights into healthy brain ageing and provide a benchmark for the study of neurodegenerative disorders such as Alzheimer's disease (AD) and frontotemporal dementia (FTD). Copyright © 2015 Elsevier Inc. All rights reserved.

Functional network alterations and their structural substrate in drug-resistant epilepsy

PubMed Central

Caciagli, Lorenzo; Bernhardt, Boris C.; Hong, Seok-Jun; Bernasconi, Andrea; Bernasconi, Neda

2014-01-01

The advent of MRI has revolutionized the evaluation and management of drug-resistant epilepsy by allowing the detection of the lesion associated with the region that gives rise to seizures. Recent evidence indicates marked chronic alterations in the functional organization of lesional tissue and large-scale cortico-subcortical networks. In this review, we focus on recent methodological developments in functional MRI (fMRI) analysis techniques and their application to the two most common drug-resistant focal epilepsies, i.e., temporal lobe epilepsy related to mesial temporal sclerosis and extra-temporal lobe epilepsy related to focal cortical dysplasia. We put particular emphasis on methodological developments in the analysis of task-free or “resting-state” fMRI to probe the integrity of intrinsic networks on a regional, inter-regional, and connectome-wide level. In temporal lobe epilepsy, these techniques have revealed disrupted connectivity of the ipsilateral mesiotemporal lobe, together with contralateral compensatory reorganization and striking reconfigurations of large-scale networks. In cortical dysplasia, initial observations indicate functional alterations in lesional, peri-lesional, and remote neocortical regions. While future research is needed to critically evaluate the reliability, sensitivity, and specificity, fMRI mapping promises to lend distinct biomarkers for diagnosis, presurgical planning, and outcome prediction. PMID:25565942

Maturation of language networks in children: A systematic review of 22years of functional MRI.

PubMed

Weiss-Croft, Louise J; Baldeweg, Torsten

2015-12-01

Understanding how language networks change during childhood is important for theories of cognitive development and for identifying the neural causes of language impairment. Despite this, there is currently little systematic evidence regarding the typical developmental trajectory for language from the field of neuroimaging. We reviewed functional MRI (fMRI) studies published between 1992 and 2014, and quantified the evidence for age-related changes in localisation and lateralisation of fMRI activation in the language network (excluding the cerebellum and subcortical regions). Although age-related changes differed according to task type and input modality, we identified four consistent findings concerning the typical maturation of the language system. First, activation in core semantic processing regions increases with age. Second, activation in lower-level sensory and motor regions increases with age as activation in higher-level control regions reduces. We suggest that this reflects increased automaticity of language processing as children become more proficient. Third, the posterior cingulate cortex and precuneus (regions associated with the default mode network) show increasing attenuation across childhood and adolescence. Finally, language lateralisation is established by approximately 5years of age. Small increases in leftward lateralisation are observed in frontal regions, but these are tightly linked to performance. Copyright © 2015 Elsevier Inc. All rights reserved.

Multilevel Deficiency of White Matter Connectivity Networks in Alzheimer's Disease: A Diffusion MRI Study with DTI and HARDI Models.

PubMed

Wang, Tao; Shi, Feng; Jin, Yan; Yap, Pew-Thian; Wee, Chong-Yaw; Zhang, Jianye; Yang, Cece; Li, Xia; Xiao, Shifu; Shen, Dinggang

2016-01-01

Alzheimer's disease (AD) is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI) to detect abnormal topological organization of white matter (WM) structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC) elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI) model and the high angular resolution diffusion imaging (HARDI) model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels.

Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction.

PubMed

Yannoutsos, Alexandra; Levy, Bernard I; Safar, Michel E; Slama, Gerard; Blacher, Jacques

2014-02-01

Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.

Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons

PubMed Central

Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew CN; Swindale, Nicholas V; Murphy, Timothy H

2017-01-01

Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps. DOI: http://dx.doi.org/10.7554/eLife.19976.001 PMID:28160463

A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics.

PubMed

McCairn, Kevin W; Nagai, Yuji; Hori, Yukiko; Ninomiya, Taihei; Kikuchi, Erika; Lee, Ju-Young; Suhara, Tetsuya; Iriki, Atsushi; Minamimoto, Takafumi; Takada, Masahiko; Isoda, Masaki; Matsumoto, Masayuki

2016-01-20

Inappropriate vocal expressions, e.g., vocal tics in Tourette syndrome, severely impact quality of life. Neural mechanisms underlying vocal tics remain unexplored because no established animal model representing the condition exists. We report that unilateral disinhibition of the nucleus accumbens (NAc) generates vocal tics in monkeys. Whole-brain PET imaging identified prominent, bilateral limbic cortico-subcortical activation. Local field potentials (LFPs) developed abnormal spikes in the NAc and the anterior cingulate cortex (ACC). Vocalization could occur without obvious LFP spikes, however, when phase-phase coupling of alpha oscillations were accentuated between the NAc, ACC, and the primary motor cortex. These findings contrasted with myoclonic motor tics induced by disinhibition of the dorsolateral putamen, where PET activity was confined to the ipsilateral sensorimotor system and LFP spikes always preceded motor tics. We propose that vocal tics emerge as a consequence of dysrhythmic alpha coupling between critical nodes in the limbic and motor networks. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

Theories of Impaired Consciousness in Epilepsy

PubMed Central

Yu, Lissa; Blumenfeld, Hal

2015-01-01

Although the precise mechanisms for control of consciousness are not fully understood, emerging data show that conscious information processing depends on the activation of certain networks in the brain and that the impairment of consciousness is related to abnormal activity in these systems. Epilepsy can lead to transient impairment of consciousness, providing a window into the mechanisms necessary for normal consciousness. Thus, despite differences in behavioral manifestations, cause, and electrophysiology, generalized tonic–clonic, absence, and partial seizures engage similar anatomical structures and pathways. We review prior concepts of impaired consciousness in epilepsy, focusing especially on temporal lobe complex partial seizures, which are a common and debilitating form of epileptic unconsciousness. We discuss a “network inhibition hypothesis” in which focal temporal lobe seizure activity disrupts normal cortical–subcortical interactions, leading to depressed neocortical function and impaired consciousness. This review of the major prior theories of impaired consciousness in epilepsy allows us to put more recent data into context and to reach a better understanding of the mechanisms important for normal consciousness. PMID:19351355

The Olfactory System Revealed: Non-Invasive Mapping by using Constrained Spherical Deconvolution Tractography in Healthy Humans

PubMed Central

Milardi, Demetrio; Cacciola, Alberto; Calamuneri, Alessandro; Ghilardi, Maria F.; Caminiti, Fabrizia; Cascio, Filippo; Andronaco, Veronica; Anastasi, Giuseppe; Mormina, Enricomaria; Arrigo, Alessandro; Bruschetta, Daniele; Quartarone, Angelo

2017-01-01

Although the olfactory sense has always been considered with less interest than the visual, auditive or somatic senses, it does plays a major role in our ordinary life, with important implication in dangerous situations or in social and emotional behaviors. Traditional Diffusion Tensor signal model and related tractography have been used in the past years to reconstruct the cranial nerves, including the olfactory nerve (ON). However, no supplementary information with regard to the pathways of the olfactory network have been provided. Here, by using the more advanced Constrained Spherical Deconvolution (CSD) diffusion model, we show for the first time in vivo and non-invasively that, in healthy humans, the olfactory system has a widely distributed anatomical network to several cortical regions as well as to many subcortical structures. Although the present study focuses on an healthy sample size, a similar approach could be applied in the near future to gain important insights with regard to the early involvement of olfaction in several neurodegenerative disorders. PMID:28443000

Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

PubMed

Febo, Marcelo; Ferris, Craig F

2014-09-11

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

An insula-frontostriatal network mediates flexible cognitive control by adaptively predicting changing control demands

PubMed Central

Jiang, Jiefeng; Beck, Jeffrey; Heller, Katherine; Egner, Tobias

2015-01-01

The anterior cingulate and lateral prefrontal cortices have been implicated in implementing context-appropriate attentional control, but the learning mechanisms underlying our ability to flexibly adapt the control settings to changing environments remain poorly understood. Here we show that human adjustments to varying control demands are captured by a reinforcement learner with a flexible, volatility-driven learning rate. Using model-based functional magnetic resonance imaging, we demonstrate that volatility of control demand is estimated by the anterior insula, which in turn optimizes the prediction of forthcoming demand in the caudate nucleus. The caudate's prediction of control demand subsequently guides the implementation of proactive and reactive attentional control in dorsal anterior cingulate and dorsolateral prefrontal cortices. These data enhance our understanding of the neuro-computational mechanisms of adaptive behaviour by connecting the classic cingulate-prefrontal cognitive control network to a subcortical control-learning mechanism that infers future demands by flexibly integrating remote and recent past experiences. PMID:26391305

Differential recruitment of the sensorimotor putamen and frontoparietal cortex during motor chunking in humans

PubMed Central

Wymbs, Nicholas F.; Bassett, Danielle S.; Mucha, Peter J.; Porter, Mason A.; Grafton, Scott T.

2012-01-01

Motor chunking facilitates movement production by combining motor elements into integrated units of behavior. Previous research suggests that chunking involves two processes: concatenation, aimed at the formation of motor-motor associations between elements or sets of elements; and segmentation, aimed at the parsing of multiple contiguous elements into shorter action sets. We used fMRI to measure the trial-wise recruitment of brain regions associated with these chunking processes as healthy subjects performed a cued sequence production task. A novel dynamic network analysis identified chunking structure for a set of motor sequences acquired during fMRI and collected on three days of training. Activity in the bilateral sensorimotor putamen positively correlated with chunk concatenation, whereas a left hemisphere frontoparietal network was correlated with chunk segmentation. Across subjects, there was an aggregate increase in chunk strength (concatenation) with training, suggesting that subcortical circuits play a direct role in the creation of fluid transitions across chunks. PMID:22681696

Network-wide reorganization of procedural memory during NREM sleep revealed by fMRI

PubMed Central

Vahdat, Shahabeddin; Fogel, Stuart; Benali, Habib; Doyon, Julien

2017-01-01

Sleep is necessary for the optimal consolidation of newly acquired procedural memories. However, the mechanisms by which motor memory traces develop during sleep remain controversial in humans, as this process has been mainly investigated indirectly by comparing pre- and post-sleep conditions. Here, we used functional magnetic resonance imaging and electroencephalography during sleep following motor sequence learning to investigate how newly-formed memory traces evolve dynamically over time. We provide direct evidence for transient reactivation followed by downscaling of functional connectivity in a cortically-dominant pattern formed during learning, as well as gradual reorganization of this representation toward a subcortically-dominant consolidated trace during non-rapid eye movement (NREM) sleep. Importantly, the putamen functional connectivity within the consolidated network during NREM sleep was related to overnight behavioral gains. Our results demonstrate that NREM sleep is necessary for two complementary processes: the restoration and reorganization of newly-learned information during sleep, which underlie human motor memory consolidation. DOI: http://dx.doi.org/10.7554/eLife.24987.001 PMID:28892464