Acute lesions that impair affective empathy

PubMed Central

Oishi, Kenichi; Hsu, John; Lindquist, Martin; Gottesman, Rebecca F.; Jarso, Samson; Crainiceanu, Ciprian; Mori, Susumu

2013-01-01

Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy—making inferences about how another person feels—engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy. PMID:23824490

Functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion in rhesus monkeys.

PubMed

Chareyron, Loïc J; Banta Lavenex, Pamela; Amaral, David G; Lavenex, Pierre

2017-12-01

Hippocampal damage in adult humans impairs episodic and semantic memory, whereas hippocampal damage early in life impairs episodic memory but leaves semantic learning relatively preserved. We have previously shown a similar behavioral dissociation in nonhuman primates. Hippocampal lesion in adult monkeys prevents allocentric spatial relational learning, whereas spatial learning persists following neonatal lesion. Here, we quantified the number of cells expressing the immediate-early gene c-fos, a marker of neuronal activity, to characterize the functional organization of the medial temporal lobe memory system following neonatal hippocampal lesion. Ninety minutes before brain collection, three control and four adult monkeys with bilateral neonatal hippocampal lesions explored a novel environment to activate brain structures involved in spatial learning. Three other adult monkeys with neonatal hippocampal lesions remained in their housing quarters. In unlesioned monkeys, we found high levels of c-fos expression in the intermediate and caudal regions of the entorhinal cortex, and in the perirhinal, parahippocampal, and retrosplenial cortices. In lesioned monkeys, spatial exploration induced an increase in c-fos expression in the intermediate field of the entorhinal cortex, the perirhinal, parahippocampal, and retrosplenial cortices, but not in the caudal entorhinal cortex. These findings suggest that different regions of the medial temporal lobe memory system may require different types of interaction with the hippocampus in support of memory. The caudal perirhinal cortex, the parahippocampal cortex, and the retrosplenial cortex may contribute to spatial learning in the absence of functional hippocampal circuits, whereas the caudal entorhinal cortex may require hippocampal output to support spatial learning.

Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy

PubMed Central

Gelinas, Jennifer N.; Khodagholy, Dion; Thesen, Thomas; Devinsky, Orrin; Buzsáki, György

2016-01-01

Interactions between the hippocampus and cortex are critical for memory. Interictal epileptiform discharges (IEDs) identify epileptic brain regions and can impair memory, but how they interact with physiological patterns of network activity is mostly undefined. We show in a rat model of temporal lobe epilepsy that spontaneous hippocampal IEDs correlate with impaired memory consolidation and are precisely coordinated with spindle oscillations in the prefrontal cortex during NREM sleep. This coordination surpasses the normal physiological ripple-spindle coupling and is accompanied by decreased ripple occurrence. IEDs also induce spindles during REM sleep and wakefulness, behavioral states that do not naturally express these oscillations, by generating a cortical ‘DOWN’ state. We confirm a similar correlation of temporofrontal IEDs with spindles over anatomically restricted cortical regions in a pilot clinical examination of four subjects with focal epilepsy. These findings imply that IEDs may impair memory via misappropriation of physiological mechanisms for hippocampal-cortical coupling, suggesting a target to treat memory impairment in epilepsy. PMID:27111281

[The neurobiology of antisocial behaviour].

PubMed

Loomans, M M; Tulen, J H M; van Marle, H J C

2010-01-01

Neuro-imaging is being used increasingly to provide explanations for antisocial behaviour. To make a neurobiological contribution to the diagnosis of many types of antisocial behaviour. The literature was searched using PubMed and combinations of the keywords 'psychopathy', 'antisocial', 'neurobiology' and 'neuro-anatomy' for the period 1990-2009. Impairments in the prefrontal cortex, amygdala, hippocampus, superior temporal gyrus, corpus callosum and anterior cingulate cortex provide a possible explanation for a large number of the symptoms associated with antisocial behaviour. The concept of psychopathy is connected mainly with impairments in a prefrontal-temporal-limbic system. CONCLUSION Combinations of deficiencies in the associated brain areas and malfunctioning of the communication between the various brain structures seem to play a more important role than deficiencies in the separate brain structures.

Auditory mismatch impairments are characterized by core neural dysfunctions in schizophrenia

PubMed Central

Gaebler, Arnim Johannes; Mathiak, Klaus; Koten, Jan Willem; König, Andrea Anna; Koush, Yury; Weyer, David; Depner, Conny; Matentzoglu, Simeon; Edgar, James Christopher; Willmes, Klaus; Zvyagintsev, Mikhail

2015-01-01

Major theories on the neural basis of schizophrenic core symptoms highlight aberrant salience network activity (insula and anterior cingulate cortex), prefrontal hypoactivation, sensory processing deficits as well as an impaired connectivity between temporal and prefrontal cortices. The mismatch negativity is a potential biomarker of schizophrenia and its reduction might be a consequence of each of these mechanisms. In contrast to the previous electroencephalographic studies, functional magnetic resonance imaging may disentangle the involved brain networks at high spatial resolution and determine contributions from localized brain responses and functional connectivity to the schizophrenic impairments. Twenty-four patients and 24 matched control subjects underwent functional magnetic resonance imaging during an optimized auditory mismatch task. Haemodynamic responses and functional connectivity were compared between groups. These data sets further entered a diagnostic classification analysis to assess impairments on the individual patient level. In the control group, mismatch responses were detected in the auditory cortex, prefrontal cortex and the salience network (insula and anterior cingulate cortex). Furthermore, mismatch processing was associated with a deactivation of the visual system and the dorsal attention network indicating a shift of resources from the visual to the auditory domain. The patients exhibited reduced activation in all of the respective systems (right auditory cortex, prefrontal cortex, and the salience network) as well as reduced deactivation of the visual system and the dorsal attention network. Group differences were most prominent in the anterior cingulate cortex and adjacent prefrontal areas. The latter regions also exhibited a reduced functional connectivity with the auditory cortex in the patients. In the classification analysis, haemodynamic responses yielded a maximal accuracy of 83% based on four features; functional connectivity data performed similarly or worse for up to about 10 features. However, connectivity data yielded a better performance when including more than 10 features yielding up to 90% accuracy. Among others, the most discriminating features represented functional connections between the auditory cortex and the anterior cingulate cortex as well as adjacent prefrontal areas. Auditory mismatch impairments incorporate major neural dysfunctions in schizophrenia. Our data suggest synergistic effects of sensory processing deficits, aberrant salience attribution, prefrontal hypoactivation as well as a disrupted connectivity between temporal and prefrontal cortices. These deficits are associated with subsequent disturbances in modality-specific resource allocation. Capturing different schizophrenic core dysfunctions, functional magnetic resonance imaging during this optimized mismatch paradigm reveals processing impairments on the individual patient level, rendering it a potential biomarker of schizophrenia. PMID:25743635

Medial perirhinal cortex disambiguates confusable objects

PubMed Central

Tyler, Lorraine K.; Monsch, Andreas U.; Taylor, Kirsten I.

2012-01-01

Our brain disambiguates the objects in our cluttered visual world seemingly effortlessly, enabling us to understand their significance and to act appropriately. The role of anteromedial temporal structures in this process, particularly the perirhinal cortex, is highly controversial. In some accounts, the perirhinal cortex is necessary for differentiating between perceptually and semantically confusable objects. Other models claim that the perirhinal cortex neither disambiguates perceptually confusable objects nor plays a unique role in semantic processing. One major hurdle to resolving this central debate is the fact that brain damage in human patients typically encompasses large portions of the anteromedial temporal lobe, such that the identification of individual substructures and precise neuroanatomical locus of the functional impairments has been difficult. We tested these competing accounts in patients with Alzheimer’s disease with varying degrees of atrophy in anteromedial structures, including the perirhinal cortex. To assess the functional contribution of each anteromedial temporal region separately, we used a detailed region of interest approach. From each participant, we obtained magnetic resonance imaging scans and behavioural data from a picture naming task that contrasted naming performance with living and non-living things as a way of manipulating perceptual and semantic confusability; living things are more similar to one another than non-living things, which have more distinctive features. We manually traced neuroanatomical regions of interest on native-space cortical surface reconstructions to obtain mean thickness estimates for the lateral and medial perirhinal cortex and entorhinal cortex. Mean cortical thickness in each region of interest, and hippocampal volume, were submitted to regression analyses predicting naming performance. Importantly, atrophy of the medial perirhinal cortex, but not lateral perirhinal cortex, entorhinal cortex or hippocampus, significantly predicted naming performance on living relative to non-living things. These findings indicate that one specific anteromedial temporal lobe region—the medial perirhinal cortex—is necessary for the disambiguation of perceptually and semantically confusable objects. Taken together, these results support a hierarchical account of object processing, whereby the perirhinal cortex at the apex of the ventral object processing system is required to bind properties of not just perceptually, but also semantically confusable objects together, enabling their disambiguation from other similar objects and thus comprehension. Significantly, this model combining a hierarchical object processing architecture with a semantic feature statistic account explains why category-specific semantic impairments for living things are associated with anteromedial temporal lobe damage, and pinpoints the root of this syndrome to perirhinal cortex damage. PMID:23250887

Deficits in temporal order memory induced by interferon-alpha (IFN-α) treatment are rescued by aerobic exercise.

PubMed

Barlow, Sally; Fahey, Briana; Smith, Kimberley J; Passecker, Johannes; Della-Chiesa, Andrea; Hok, Vincent; Day, Jennifer S; Callaghan, Charlotte K; O'Mara, Shane M

2018-05-18

Patients receiving cytokine immunotherapy with IFN-α frequently present with neuropsychiatric consequences and cognitive impairments, including a profound depressive-like symptomatology. While the neurobiological substrates of the dysfunction that leads to adverse events in IFN-α-treated patients remains ill-defined, dysfunctions of the hippocampus and prefrontal cortex (PFC) are strong possibilities. To date, hippocampal deficits have been well-characterised; there does however remain a lack of insight into the nature of prefrontal participation. Here, we used a PFC-supported temporal order memory paradigm to examine if IFN-α treatment induced deficits in performance; additionally, we used an object recognition task to assess the integrity of the perirhinal cortex (PRH). Finally, the utility of exercise as an ameliorative strategy to recover temporal order deficits in rats was also explored. We found that IFN-α-treatment impaired temporal order memory discriminations, whereas recognition memory remained intact, reflecting a possible dissociation between recognition and temporal order memory processing. Further characterisation of temporal order memory impairments using a longitudinal design revealed that deficits persisted for 10 weeks following cessation of IFN-α-treatment. Finally, a 6 week forced exercise regime reversed IFN-α-induced deficits in temporal order memory. These data provide further insight into the circuitry involved in cognitive impairments arising from IFN-α-treatment. Here we suggest that PFC (or the hippocampo-prefrontal pathway) may be compromised whilst the function of the PRH is preserved. Deficits may persist after cessation of IFN-α-treatment which suggests that extended patient monitoring is required. Aerobic exercise may be restorative and could prove beneficial for patients treated with IFN-α. Copyright © 2018 Elsevier Inc. All rights reserved.

Stimulus familiarity modulates functional connectivity of the perirhinal cortex and anterior hippocampus during visual discrimination of faces and objects

PubMed Central

McLelland, Victoria C.; Chan, David; Ferber, Susanne; Barense, Morgan D.

2014-01-01

Recent research suggests that the medial temporal lobe (MTL) is involved in perception as well as in declarative memory. Amnesic patients with focal MTL lesions and semantic dementia patients showed perceptual deficits when discriminating faces and objects. Interestingly, these two patient groups showed different profiles of impairment for familiar and unfamiliar stimuli. For MTL amnesics, the use of familiar relative to unfamiliar stimuli improved discrimination performance. By contrast, patients with semantic dementia—a neurodegenerative condition associated with anterolateral temporal lobe damage—showed no such facilitation from familiar stimuli. Given that the two patient groups had highly overlapping patterns of damage to the perirhinal cortex, hippocampus, and temporal pole, the neuroanatomical substrates underlying their performance discrepancy were unclear. Here, we addressed this question with a multivariate reanalysis of the data presented by Barense et al. (2011), using functional connectivity to examine how stimulus familiarity affected the broader networks with which the perirhinal cortex, hippocampus, and temporal poles interact. In this study, healthy participants were scanned while they performed an odd-one-out perceptual task involving familiar and novel faces or objects. Seed-based analyses revealed that functional connectivity of the right perirhinal cortex and right anterior hippocampus was modulated by the degree of stimulus familiarity. For familiar relative to unfamiliar faces and objects, both right perirhinal cortex and right anterior hippocampus showed enhanced functional correlations with anterior/lateral temporal cortex, temporal pole, and medial/lateral parietal cortex. These findings suggest that in order to benefit from stimulus familiarity, it is necessary to engage not only the perirhinal cortex and hippocampus, but also a network of regions known to represent semantic information. PMID:24624075

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

Radiological Evaluation of Strategic Structures in Patients with Mild Cognitive Impairment and Early Alzheimer's Disease.

PubMed

Nesteruk, Tomasz; Nesteruk, Marta; Styczyńska, Maria; Barcikowska-Kotowicz, Maria; Walecki, Jerzy

2016-01-01

The aim of the study was to evaluate the diagnostic value of two measurement techniques in patients with cognitive impairment - automated volumetry of the hippocampus, entorhinal cortex, parahippocampal gyrus, posterior cingulate gyrus, cortex of the temporal lobes and corpus callosum, and fractional anisotropy (FA) index measurement of the corpus callosum using diffusion tensor imaging. A total number of 96 patients underwent magnetic resonance imaging study of the brain - 33 healthy controls (HC), 33 patients with diagnosed mild cognitive impairment (MCI) and 30 patients with Alzheimer's disease (AD) in early stage. The severity of the dementia was evaluated with neuropsychological test battery. The volumetric measurements were performed automatically using FreeSurfer imaging software. The measurements of FA index were performed manually using ROI (region of interest) tool. The volumetric measurement of the temporal lobe cortex had the highest correct classification rate (68.7%), whereas the lowest was achieved with FA index measurement of the corpus callosum (51%). The highest sensitivity and specificity in discriminating between the patients with MCI vs. early AD was achieved with the volumetric measurement of the corpus callosum - the values were 73% and 71%, respectively, and the correct classification rate was 72%. The highest sensitivity and specificity in discriminating between HC and the patients with early AD was achieved with the volumetric measurement of the entorhinal cortex - the values were 94% and 100%, respectively, and the correct classification rate was 97%. The highest sensitivity and specificity in discriminating between HC and the patients with MCI was achieved with the volumetric measurement of the temporal lobe cortex - the values were 90% and 93%, respectively, and the correct classification rate was 92%. The diagnostic value varied depending on the measurement technique. The volumetric measurement of the atrophy proved to be the best imaging biomarker, which allowed the distinction between the groups of patients. The volumetric assessment of the corpus callosum proved to be a useful tool in discriminating between the patients with MCI vs. early AD.

Functional response in ventral temporal cortex differentiates mild cognitive impairment from normal aging

PubMed Central

Gold, Brian T.; Jiang, Yang; Jicha, Greg A.; Smith, Charles D.

2010-01-01

The present study sought to identify altered brain activation patterns in amnestic mild cognitive impairment (MCI) that could precede frank task impairment and neocortical atrophy. A high accuracy lexical decision (LD) task was therefore employed. Both MCI and normal senior (NS) groups completed the LD task while functional magnetic resonance imaging (fMRI) was performed. Accuracy on the LD task was high (≥ 89% correct for both groups), and both groups activated a network of occipitotemporal regions and inferior frontal cortex. However, compared to the NS group, the MCI group showed reduced fMRI activation in these regions and increased activation in bilateral portions of anterior cingluate cortex. Results from a voxel-based morphometry analysis indicate that altered activations in the MCI group were not within regions of atrophy. Receiver operating characteristic curves demonstrate that reduced fMRI response in the left and right mid-fusiform gyri accurately discriminate MCI from NS. When activation magnitude in both fusiform gyri were included in a single logistic regression model, group classification accuracy was very high (area under the curve = 0.93). These results show that a disrupted functional response in the ventral temporal lobe accurately distinguishes individuals with MCI from normal seniors, a finding which may have implications for identifying seniors at risk for cognitive decline. PMID:20063353

Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex.

PubMed

Jonas, Jacques; Frismand, Solène; Vignal, Jean-Pierre; Colnat-Coulbois, Sophie; Koessler, Laurent; Vespignani, Hervé; Rossion, Bruno; Maillard, Louis

2014-07-01

Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low-intensity with depth electrodes implanted in the occipito-parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito-parieto-temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Copyright © 2013 Wiley Periodicals, Inc.

Cortical Thickness Abnormalities in Late Adolescence with Online Gaming Addiction

PubMed Central

Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M.; Liu, Yijun; Qin, Wei; Tian, Jie

2013-01-01

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction. PMID:23326379

Cortical thickness abnormalities in late adolescence with online gaming addiction.

PubMed

Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M; Liu, Yijun; Qin, Wei; Tian, Jie

2013-01-01

Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

Decreased prefrontal cortical dopamine transmission in alcoholism.

PubMed

Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

2014-08-01

Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

Lesion correlates of impairments in actual tool use following unilateral brain damage.

PubMed

Salazar-López, E; Schwaiger, B J; Hermsdörfer, J

2016-04-01

To understand how the brain controls actions involving tools, tests have been developed employing different paradigms such as pantomime, imitation and real tool use. The relevant areas have been localized in the premotor cortex, the middle temporal gyrus and the superior and inferior parietal lobe. This study employs Voxel Lesion Symptom Mapping to relate the functional impairment in actual tool use with extent and localization of the structural damage in the left (LBD, N=31) and right (RBD, N=19) hemisphere in chronic stroke patients. A series of 12 tools was presented to participants in a carousel. In addition, a non-tool condition tested the prescribed manipulation of a bar. The execution was scored according to an apraxic error scale based on the dimensions grasp, movement, direction and space. Results in the LBD group show that the ventro-dorsal stream constitutes the core of the defective network responsible for impaired tool use; it is composed of the inferior parietal lobe, the supramarginal and angular gyrus and the dorsal premotor cortex. In addition, involvement of regions in the temporal lobe, the rolandic operculum, the ventral premotor cortex and the middle occipital gyrus provide evidence of the role of the ventral stream in this task. Brain areas related to the use of the bar largely overlapped with this network. For patients with RBD data were less conclusive; however, a trend for the involvement of the temporal lobe in apraxic errors was manifested. Skilled bar manipulation depended on the same temporal area in these patients. Therefore, actual tool use depends on a well described left fronto-parietal-temporal network. RBD affects actual tool use, however the underlying neural processes may be more widely distributed and more heterogeneous. Goal directed manipulation of non-tool objects seems to involve very similar brain areas as tool use, suggesting that both types of manipulation share identical processes and neural representations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Temporally flexible feedback signal to foveal cortex for peripheral object recognition

PubMed Central

Fan, Xiaoxu; Wang, Lan; Shao, Hanyu; Kersten, Daniel; He, Sheng

2016-01-01

Recent studies have shown that information from peripherally presented images is present in the human foveal retinotopic cortex, presumably because of feedback signals. We investigated this potential feedback signal by presenting noise in fovea at different object–noise stimulus onset asynchronies (SOAs), whereas subjects performed a discrimination task on peripheral objects. Results revealed a selective impairment of performance when foveal noise was presented at 250-ms SOA, but only for tasks that required comparing objects’ spatial details, suggesting a task- and stimulus-dependent foveal processing mechanism. Critically, the temporal window of foveal processing was shifted when mental rotation was required for the peripheral objects, indicating that the foveal retinotopic processing is not automatically engaged at a fixed time following peripheral stimulation; rather, it occurs at a stage when detailed information is required. Moreover, fMRI measurements using multivoxel pattern analysis showed that both image and object category-relevant information of peripheral objects was represented in the foveal cortex. Taken together, our results support the hypothesis of a temporally flexible feedback signal to the foveal retinotopic cortex when discriminating objects in the visual periphery. PMID:27671651

A voxel-based lesion study on facial emotion recognition after penetrating brain injury

PubMed Central

Dal Monte, Olga; Solomon, Jeffrey M.; Schintu, Selene; Knutson, Kristine M.; Strenziok, Maren; Pardini, Matteo; Leopold, Anne; Raymont, Vanessa; Grafman, Jordan

2013-01-01

The ability to read emotions in the face of another person is an important social skill that can be impaired in subjects with traumatic brain injury (TBI). To determine the brain regions that modulate facial emotion recognition, we conducted a whole-brain analysis using a well-validated facial emotion recognition task and voxel-based lesion symptom mapping (VLSM) in a large sample of patients with focal penetrating TBIs (pTBIs). Our results revealed that individuals with pTBI performed significantly worse than normal controls in recognizing unpleasant emotions. VLSM mapping results showed that impairment in facial emotion recognition was due to damage in a bilateral fronto-temporo-limbic network, including medial prefrontal cortex (PFC), anterior cingulate cortex, left insula and temporal areas. Beside those common areas, damage to the bilateral and anterior regions of PFC led to impairment in recognizing unpleasant emotions, whereas bilateral posterior PFC and left temporal areas led to impairment in recognizing pleasant emotions. Our findings add empirical evidence that the ability to read pleasant and unpleasant emotions in other people's faces is a complex process involving not only a common network that includes bilateral fronto-temporo-limbic lobes, but also other regions depending on emotional valence. PMID:22496440

Nonverbal auditory agnosia with lesion to Wernicke's area.

PubMed

Saygin, Ayse Pinar; Leech, Robert; Dick, Frederic

2010-01-01

We report the case of patient M, who suffered unilateral left posterior temporal and parietal damage, brain regions typically associated with language processing. Language function largely recovered since the infarct, with no measurable speech comprehension impairments. However, the patient exhibited a severe impairment in nonverbal auditory comprehension. We carried out extensive audiological and behavioral testing in order to characterize M's unusual neuropsychological profile. We also examined the patient's and controls' neural responses to verbal and nonverbal auditory stimuli using functional magnetic resonance imaging (fMRI). We verified that the patient exhibited persistent and severe auditory agnosia for nonverbal sounds in the absence of verbal comprehension deficits or peripheral hearing problems. Acoustical analyses suggested that his residual processing of a minority of environmental sounds might rely on his speech processing abilities. In the patient's brain, contralateral (right) temporal cortex as well as perilesional (left) anterior temporal cortex were strongly responsive to verbal, but not to nonverbal sounds, a pattern that stands in marked contrast to the controls' data. This substantial reorganization of auditory processing likely supported the recovery of M's speech processing.

A case of musical anhedonia due to right putaminal hemorrhage: a disconnection syndrome between the auditory cortex and insula.

PubMed

Satoh, Masayuki; Kato, Natsuko; Tabei, Ken-Ichi; Nakano, Chizuru; Abe, Makiko; Fujita, Risa; Kida, Hirotaka; Tomimoto, Hidekazu; Kondo, Kiyohiko

2016-12-01

A 63-year-old, right-handed professional chorus conductor developed right putaminal hemorrhage, and became unable to experience emotion while listening to music. Two years later, neurological examination revealed slight left hemiparesis. Neuromusicological assessments revealed impaired judgment of "musical sense," and the inability to discriminate the sound of chords in pure intervals from those in equal temperament. Brain MRI and tractography identified the old hemorrhagic lesion in the right putamen and impaired fiber connectivity between the right insula and superior temporal lobe. These findings suggest that musical anhedonia might be caused by a disconnection between the insula and auditory cortex.

Treatment for Alexia with Agraphia Following Left Ventral Occipito-Temporal Damage: Strengthening Orthographic Representations Common to Reading and Spelling

ERIC Educational Resources Information Center

Kim, Esther S.; Rising, Kindle; Rapcsak, Steven Z.; Beeson, Pélagie M.

2015-01-01

Purpose: Damage to left ventral occipito-temporal cortex can give rise to written language impairment characterized by pure alexia/letter-by-letter (LBL) reading, as well as surface alexia and agraphia. The purpose of this study was to examine the therapeutic effects of a combined treatment approach to address concurrent LBL reading with surface…

A selective impairment of perception of sound motion direction in peripheral space: A case study.

PubMed

Thaler, Lore; Paciocco, Joseph; Daley, Mark; Lesniak, Gabriella D; Purcell, David W; Fraser, J Alexander; Dutton, Gordon N; Rossit, Stephanie; Goodale, Melvyn A; Culham, Jody C

2016-01-08

It is still an open question if the auditory system, similar to the visual system, processes auditory motion independently from other aspects of spatial hearing, such as static location. Here, we report psychophysical data from a patient (female, 42 and 44 years old at the time of two testing sessions), who suffered a bilateral occipital infarction over 12 years earlier, and who has extensive damage in the occipital lobe bilaterally, extending into inferior posterior temporal cortex bilaterally and into right parietal cortex. We measured the patient's spatial hearing ability to discriminate static location, detect motion and perceive motion direction in both central (straight ahead), and right and left peripheral auditory space (50° to the left and right of straight ahead). Compared to control subjects, the patient was impaired in her perception of direction of auditory motion in peripheral auditory space, and the deficit was more pronounced on the right side. However, there was no impairment in her perception of the direction of auditory motion in central space. Furthermore, detection of motion and discrimination of static location were normal in both central and peripheral space. The patient also performed normally in a wide battery of non-spatial audiological tests. Our data are consistent with previous neuropsychological and neuroimaging results that link posterior temporal cortex and parietal cortex with the processing of auditory motion. Most importantly, however, our data break new ground by suggesting a division of auditory motion processing in terms of speed and direction and in terms of central and peripheral space. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mismatch Negativity in Recent-Onset and Chronic Schizophrenia: A Current Source Density Analysis

PubMed Central

Fulham, W. Ross; Michie, Patricia T.; Ward, Philip B.; Rasser, Paul E.; Todd, Juanita; Johnston, Patrick J.; Thompson, Paul M.; Schall, Ulrich

2014-01-01

Mismatch negativity (MMN) is a component of the event-related potential elicited by deviant auditory stimuli. It is presumed to index pre-attentive monitoring of changes in the auditory environment. MMN amplitude is smaller in groups of individuals with schizophrenia compared to healthy controls. We compared duration-deviant MMN in 16 recent-onset and 19 chronic schizophrenia patients versus age- and sex-matched controls. Reduced frontal MMN was found in both patient groups, involved reduced hemispheric asymmetry, and was correlated with Global Assessment of Functioning (GAF) and negative symptom ratings. A cortically-constrained LORETA analysis, incorporating anatomical data from each individual's MRI, was performed to generate a current source density model of the MMN response over time. This model suggested MMN generation within a temporal, parietal and frontal network, which was right hemisphere dominant only in controls. An exploratory analysis revealed reduced CSD in patients in superior and middle temporal cortex, inferior and superior parietal cortex, precuneus, anterior cingulate, and superior and middle frontal cortex. A region of interest (ROI) analysis was performed. For the early phase of the MMN, patients had reduced bilateral temporal and parietal response and no lateralisation in frontal ROIs. For late MMN, patients had reduced bilateral parietal response and no lateralisation in temporal ROIs. In patients, correlations revealed a link between GAF and the MMN response in parietal cortex. In controls, the frontal response onset was 17 ms later than the temporal and parietal response. In patients, onset latency of the MMN response was delayed in secondary, but not primary, auditory cortex. However amplitude reductions were observed in both primary and secondary auditory cortex. These latency delays may indicate relatively intact information processing upstream of the primary auditory cortex, but impaired primary auditory cortex or cortico-cortical or thalamo-cortical communication with higher auditory cortices as a core deficit in schizophrenia. PMID:24949859

Retrograde amnesia in patients with hippocampal, medial temporal, temporal lobe, or frontal pathology.

PubMed

Bright, Peter; Buckman, Joseph; Fradera, Alex; Yoshimasu, Haruo; Colchester, Alan C F; Kopelman, Michael D

2006-01-01

There is considerable controversy concerning the theoretical basis of retrograde amnesia (R.A.). In the present paper, we compare medial temporal, medial plus lateral temporal, and frontal lesion patients on a new autobiographical memory task and measures of the more semantic aspects of memory (famous faces and news events). Only those patients with damage extending beyond the medial temporal cortex into the lateral temporal regions showed severe impairment on free recall remote memory tasks, and this held for both the autobiographical and the more semantic memory tests. However, on t-test analysis, the medial temporal group was impaired in retrieving recent autobiographical memories. Within the medial temporal group, those patients who had combined hippocampal and parahippocampal atrophy (H+) on quantified MRI performed somewhat worse on the semantic tasks than those with atrophy confined to the hippocampi (H-), but scores were very similar on autobiographical episodic recall. Correlational analyses with regional MRI volumes showed that lateral temporal volume was correlated significantly with performance on all three retrograde amnesia tests. The findings are discussed in terms of consolidation, reconsolidation, and multiple trace theory: We suggest that a widely distributed network of regions underlies the retrieval of past memories, and that the extent of lateral temporal damage appears to be critical to the emergence of a severe remote memory impairment.

Dorsolateral prefrontal lesions do not impair tests of scene learning and decision-making that require frontal–temporal interaction

PubMed Central

Baxter, Mark G; Gaffan, David; Kyriazis, Diana A; Mitchell, Anna S

2008-01-01

Theories of dorsolateral prefrontal cortex (DLPFC) involvement in cognitive function variously emphasize its involvement in rule implementation, cognitive control, or working and/or spatial memory. These theories predict broad effects of DLPFC lesions on tests of visual learning and memory. We evaluated the effects of DLPFC lesions (including both banks of the principal sulcus) in rhesus monkeys on tests of scene learning and strategy implementation that are severely impaired following crossed unilateral lesions of frontal cortex and inferotemporal cortex. Dorsolateral lesions had no effect on learning of new scene problems postoperatively, or on the implementation of preoperatively acquired strategies. They were also without effect on the ability to adjust choice behaviour in response to a change in reinforcer value, a capacity that requires interaction between the amygdala and frontal lobe. These intact abilities following DLPFC damage support specialization of function within the prefrontal cortex, and suggest that many aspects of memory and strategic and goal-directed behaviour can survive ablation of this structure. PMID:18702721

Contributions of Low and High Spatial Frequency Processing to Impaired Object Recognition Circuitry in Schizophrenia

PubMed Central

Calderone, Daniel J.; Hoptman, Matthew J.; Martínez, Antígona; Nair-Collins, Sangeeta; Mauro, Cristina J.; Bar, Moshe; Javitt, Daniel C.; Butler, Pamela D.

2013-01-01

Patients with schizophrenia exhibit cognitive and sensory impairment, and object recognition deficits have been linked to sensory deficits. The “frame and fill” model of object recognition posits that low spatial frequency (LSF) information rapidly reaches the prefrontal cortex (PFC) and creates a general shape of an object that feeds back to the ventral temporal cortex to assist object recognition. Visual dysfunction findings in schizophrenia suggest a preferential loss of LSF information. This study used functional magnetic resonance imaging (fMRI) and resting state functional connectivity (RSFC) to investigate the contribution of visual deficits to impaired object “framing” circuitry in schizophrenia. Participants were shown object stimuli that were intact or contained only LSF or high spatial frequency (HSF) information. For controls, fMRI revealed preferential activation to LSF information in precuneus, superior temporal, and medial and dorsolateral PFC areas, whereas patients showed a preference for HSF information or no preference. RSFC revealed a lack of connectivity between early visual areas and PFC for patients. These results demonstrate impaired processing of LSF information during object recognition in schizophrenia, with patients instead displaying increased processing of HSF information. This is consistent with findings of a preference for local over global visual information in schizophrenia. PMID:22735157

The Earliest Stage of Cognitive Impairment in Transition From Normal Aging to Alzheimer Disease Is Marked By Prominent RNA Oxidation in Vulnerable Neurons

PubMed Central

Nunomura, Akihiko; Tamaoki, Toshio; Motohashi, Nobutaka; Nakamura, Masao; McKeel, Daniel W.; Tabaton, Massimo; Lee, Hyoung-gon; Smith, Mark A.; Perry, George; Zhu, Xiongwei

2012-01-01

Although neuronal RNA oxidation is a prominent and established feature in age-associated neurodegenerative disorders such as Alzheimer disease (AD), oxidative damage to neuronal RNA in aging and in the transitional stages from normal elderly to the onset of AD has not been fully examined. In this study, we used an in situ approach to identify an oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the cerebral cortex of 65 individuals without dementia ranging in age from 0.3 to 86 years. We also examined brain samples from 20 elderly who were evaluated for their premortem clinical dementia rating score and postmortem brain pathological diagnoses to investigate preclinical AD and mild cognitive impairment. Relative density measurements of 8OHG-immunoreactivity revealed a statistically significant increase in neuronal RNA oxidation during aging in the hippocampus and the temporal neocortex. In subjects with mild cognitive impairment but not preclinical AD, neurons of the temporal cortex showed a higher burden of oxidized RNA compared to age-matched controls. These results indicate that although neuronal RNA oxidation fundamentally occurs as an age-associated phenomenon, more prominent RNA damage than in normal aging correlates with the onset of cognitive impairment in the prodromal stage of AD. PMID:22318126

The medial prefrontal cortex-lateral entorhinal cortex circuit is essential for episodic-like memory and associative object-recognition.

PubMed

Chao, Owen Y; Huston, Joseph P; Li, Jay-Shake; Wang, An-Li; de Souza Silva, Maria A

2016-05-01

The prefrontal cortex directly projects to the lateral entorhinal cortex (LEC), an important substrate for engaging item-associated information and relaying the information to the hippocampus. Here we ask to what extent the communication between the prefrontal cortex and LEC is critically involved in the processing of episodic-like memory. We applied a disconnection procedure to test whether the interaction between the medial prefrontal cortex (mPFC) and LEC is essential for the expression of recognition memory. It was found that male rats that received unilateral NMDA lesions of the mPFC and LEC in the same hemisphere, exhibited intact episodic-like (what-where-when) and object-recognition memories. When these lesions were placed in the opposite hemispheres (disconnection), episodic-like and associative memories for object identity, location and context were impaired. However, the disconnection did not impair the components of episodic memory, namely memory for novel object (what), object place (where) and temporal order (when), per se. Thus, the present findings suggest that the mPFC and LEC are a critical part of a neural circuit that underlies episodic-like and associative object-recognition memory. © 2015 Wiley Periodicals, Inc.

Reduced Cortical Thickness in Mental Retardation

PubMed Central

Wang, Chao; Wang, Jiaojian; Zhang, Yun; Yu, Chunshui; Jiang, Tianzi

2011-01-01

Mental retardation is a developmental disorder associated with impaired cognitive functioning and deficits in adaptive behaviors. Many studies have addressed white matter abnormalities in patients with mental retardation, while the changes of the cerebral cortex have been studied to a lesser extent. Quantitative analysis of cortical integrity using cortical thickness measurement may provide new insights into the gray matter pathology. In this study, cortical thickness was compared between 13 patients with mental retardation and 26 demographically matched healthy controls. We found that patients with mental retardation had significantly reduced cortical thickness in multiple brain regions compared with healthy controls. These regions include the bilateral lingual gyrus, the bilateral fusiform gyrus, the bilateral parahippocampal gyrus, the bilateral temporal pole, the left inferior temporal gyrus, the right lateral orbitofrontal cortex and the right precentral gyrus. The observed cortical thickness reductions might be the anatomical substrates for the impaired cognitive functioning and deficits in adaptive behaviors in patients with mental retardation. Cortical thickness measurement might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications. PMID:22216343

Brain abnormalities in antisocial individuals: implications for the law.

PubMed

Yang, Yaling; Glenn, Andrea L; Raine, Adrian

2008-01-01

With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala-hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making. (c) 2008 John Wiley & Sons, Ltd.

Pre-dementia memory impairment is associated with white matter tract affection.

PubMed

Grambaite, Ramune; Reinvang, Ivar; Selnes, Per; Fjell, Anders M; Walhovd, Kristine B; Stenset, Vidar; Fladby, Tormod

2011-01-01

Mild cognitive impairment (MCI), especially amnestic, often represents pre-dementia Alzheimer's disease, characterized by medial temporal lobe atrophy, while white matter (WM) alterations are insufficiently described. We analyze both cortical morphometric and WM diffusivity differences in amnestic versus non-amnestic subtypes and ask if memory and WM tract affection are related independently of cortical atrophy. Forty-nine patients from a university-hospital based memory clinic with a score of 3 on the Global Deterioration Scale aged 43-77 years (45% female) were included. Two neuropsychologists have classified cases as amnestic (aMCI), non-amnestic (naMCI), or less advanced (laMCI), not satisfying criteria for aMCI/naMCI. Diffusion tensor imaging (DTI) WM tract and morphometric data of the temporal-parietal memory network were compared among patient subtypes and related to story, word list, and visual memory. WM radial and mean diffusivity (DR and MD), underlying the entorhinal cortex, were higher in aMCI compared with laMCI. WM DR and MD, underlying the entorhinal, parahippocampal, and middle temporal cortex, explained unique variance in word list and story memory, and this was not due to secondary effects of cortical thinning. DTI may thus potentially aid diagnosis in early disease stages. ).

Theory of mind and frontal lobe pathology in schizophrenia: a voxel-based morphometry study.

PubMed

Hirao, Kazuyuki; Miyata, Jun; Fujiwara, Hironobu; Yamada, Makiko; Namiki, Chihiro; Shimizu, Mitsuaki; Sawamoto, Nobukatsu; Fukuyama, Hidenao; Hayashi, Takuji; Murai, Toshiya

2008-10-01

Impaired ability to infer the mental states of others (theory of mind; ToM) is considered to be a key contributor to the poor social functioning of patients with schizophrenia. Although neuroimaging and lesion studies have provided empirical evidence for the neural basis of ToM ability, including the involvement of several prefrontal and temporal structures, the association between pathology of these structures and ToM impairment in schizophrenia patients is less well understood. To address this issue, we investigated structural brain abnormalities and ToM impairment in patients with schizophrenia, and examined the relationship between them. Twenty schizophrenia patients and 20 age-, sex- and education-matched healthy participants underwent magnetic resonance imaging (MRI) and were examined for ToM ability based on the revised version of the "Reading the Mind in the Eyes" (or Eyes) test [Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., Plumb, I., 2001. The 'Reading the Mind in the Eyes' test revised version: A study with normal adults, and adults with Asperger syndrome or high-functioning autism. J. Child Psychol. Psychiatry 42, 241-251]. Voxel-based morphometry (VBM) was performed to investigate regional brain alterations. Relative to normal controls, schizophrenia patients exhibited gray matter reductions in the dorsomedial prefrontal cortex (DMPFC), left ventrolateral prefrontal cortex (VLPFC), ventromedial prefrontal cortex (VMPFC), anterior cingulate cortex (ACC), right superior temporal gyrus (STG) and right insula. The patients performed poorly on the Eyes test. Importantly, poor performance on the Eyes test was found to be associated with gray matter reduction in the left VLPFC in the patient group. These results suggest that prefrontal cortical reduction, especially in the left VLPFC, is a key pathology underlying the difficulties faced by schizophrenia patients in inferring the mental states of others.

Neural Correlates of Temporal Complexity and Synchrony during Audiovisual Correspondence Detection.

PubMed

Baumann, Oliver; Vromen, Joyce M G; Cheung, Allen; McFadyen, Jessica; Ren, Yudan; Guo, Christine C

2018-01-01

We often perceive real-life objects as multisensory cues through space and time. A key challenge for audiovisual integration is to match neural signals that not only originate from different sensory modalities but also that typically reach the observer at slightly different times. In humans, complex, unpredictable audiovisual streams lead to higher levels of perceptual coherence than predictable, rhythmic streams. In addition, perceptual coherence for complex signals seems less affected by increased asynchrony between visual and auditory modalities than for simple signals. Here, we used functional magnetic resonance imaging to determine the human neural correlates of audiovisual signals with different levels of temporal complexity and synchrony. Our study demonstrated that greater perceptual asynchrony and lower signal complexity impaired performance in an audiovisual coherence-matching task. Differences in asynchrony and complexity were also underpinned by a partially different set of brain regions. In particular, our results suggest that, while regions in the dorsolateral prefrontal cortex (DLPFC) were modulated by differences in memory load due to stimulus asynchrony, areas traditionally thought to be involved in speech production and recognition, such as the inferior frontal and superior temporal cortex, were modulated by the temporal complexity of the audiovisual signals. Our results, therefore, indicate specific processing roles for different subregions of the fronto-temporal cortex during audiovisual coherence detection.

Neural Correlates of Temporal Complexity and Synchrony during Audiovisual Correspondence Detection

PubMed Central

Ren, Yudan

2018-01-01

Abstract We often perceive real-life objects as multisensory cues through space and time. A key challenge for audiovisual integration is to match neural signals that not only originate from different sensory modalities but also that typically reach the observer at slightly different times. In humans, complex, unpredictable audiovisual streams lead to higher levels of perceptual coherence than predictable, rhythmic streams. In addition, perceptual coherence for complex signals seems less affected by increased asynchrony between visual and auditory modalities than for simple signals. Here, we used functional magnetic resonance imaging to determine the human neural correlates of audiovisual signals with different levels of temporal complexity and synchrony. Our study demonstrated that greater perceptual asynchrony and lower signal complexity impaired performance in an audiovisual coherence-matching task. Differences in asynchrony and complexity were also underpinned by a partially different set of brain regions. In particular, our results suggest that, while regions in the dorsolateral prefrontal cortex (DLPFC) were modulated by differences in memory load due to stimulus asynchrony, areas traditionally thought to be involved in speech production and recognition, such as the inferior frontal and superior temporal cortex, were modulated by the temporal complexity of the audiovisual signals. Our results, therefore, indicate specific processing roles for different subregions of the fronto-temporal cortex during audiovisual coherence detection. PMID:29354682

Dynamic diaschisis: anatomically remote and context-sensitive human brain lesions.

PubMed

Price, C J; Warburton, E A; Moore, C J; Frackowiak, R S; Friston, K J

2001-05-15

Functional neuroimaging was used to investigate how lesions to the Broca's area impair neuronal responses in remote undamaged cortical regions. Four patients with speech output problems, but relatively preserved comprehension, were scanned while viewing words relative to consonant letter strings. In normal subjects, this results in left lateralized activation in the posterior inferior frontal, middle temporal, and posterior inferior temporal cortices. Each patient activated normally in the middle temporal region but abnormally in the damaged posterior inferior frontal cortex and the undamaged posterior inferior temporal cortex. In the damaged frontal region, activity was insensitive to the presence of words but in the undamaged posterior inferior temporal region, activity decreased in the presence of words rather than increasing as it did in the normal individuals. The reversal of responses in the left posterior inferior temporal region illustrate the context-sensitive nature of the abnormality and that failure to activate the left posterior temporal region could not simply be accounted for by insufficient demands on the underlying function. We propose that, in normal individuals, visual word presentation changes the effective connectivity among reading areas and, in patients, posterior temporal responses are abnormal when they depend upon inputs from the damaged inferior frontal cortex. Our results serve to introduce the concept of dynamic diaschisis; the anatomically remote and context-sensitive effects of focal brain lesions. Dynamic diaschisis reveals abnormalities of functional integration that may have profound implications for neuropsychological inference, functional anatomy and, vicariously, cognitive rehabilitation.

Minocycline prevents Abeta(25-35)-induced reduction of somatostatin and neprilysin content in rat temporal cortex.

PubMed

Burgos-Ramos, E; Puebla-Jiménez, L; Arilla-Ferreiro, E

2009-02-13

Tetracyclines have been demonstrated to inhibit formation of beta-amyloid (Abeta) aggregates and to disassemble preformed fibrils. Minocycline, a semi-synthetic second-generation tetracycline, can reverse Abeta-induced impairment of cognitive functions. Since somatostatin is involved in cognition and we recently showed that Abeta(25-35) lowers somatostatin expression in the rat temporal cortex, our aim here was to analyze the effects of minocycline on somatostatin immunoreactivity and mRNA levels in the temporal cortex of Abeta(25-35)-infused and healthy rats. Moreover, since brain levels of neprilysin, an Abeta-degrading enzyme, decrease with age, favoring the appearance of senile neuritic plaques, we tested whether minocyline could affect neprilysin expression. Wistar rats were thus injected with minocycline twice on the first day of treatment. On the following day, and during 14 days, Abeta(25-35) or vehicle were administered. Minocycline was injected once again on days 13 and 14. All animals were sacrificed 24 h after the last drug injection. Minocycline abrogated the Abeta(25-35)-induced decrease of somatostatin-like immunoreactive content, somatostatin mRNA levels, phosphorylated-CREB content and neprilysin levels. Minocycline alone enhanced these targets. Our findings indicate that minocycline prevents the deleterious effects of Abeta(25-35) on SRIF and neprilysin expression in the rat temporal cortex and that it has protective effects per se on these parameters.

Pitch-Responsive Cortical Regions in Congenital Amusia.

PubMed

Norman-Haignere, Sam V; Albouy, Philippe; Caclin, Anne; McDermott, Josh H; Kanwisher, Nancy G; Tillmann, Barbara

2016-03-09

Congenital amusia is a lifelong deficit in music perception thought to reflect an underlying impairment in the perception and memory of pitch. The neural basis of amusic impairments is actively debated. Some prior studies have suggested that amusia stems from impaired connectivity between auditory and frontal cortex. However, it remains possible that impairments in pitch coding within auditory cortex also contribute to the disorder, in part because prior studies have not measured responses from the cortical regions most implicated in pitch perception in normal individuals. We addressed this question by measuring fMRI responses in 11 subjects with amusia and 11 age- and education-matched controls to a stimulus contrast that reliably identifies pitch-responsive regions in normal individuals: harmonic tones versus frequency-matched noise. Our findings demonstrate that amusic individuals with a substantial pitch perception deficit exhibit clusters of pitch-responsive voxels that are comparable in extent, selectivity, and anatomical location to those of control participants. We discuss possible explanations for why amusics might be impaired at perceiving pitch relations despite exhibiting normal fMRI responses to pitch in their auditory cortex: (1) individual neurons within the pitch-responsive region might exhibit abnormal tuning or temporal coding not detectable with fMRI, (2) anatomical tracts that link pitch-responsive regions to other brain areas (e.g., frontal cortex) might be altered, and (3) cortical regions outside of pitch-responsive cortex might be abnormal. The ability to identify pitch-responsive regions in individual amusic subjects will make it possible to ask more precise questions about their role in amusia in future work. Copyright © 2016 the authors 0270-6474/16/362986-09$15.00/0.

Predicted sequence of cortical tau and amyloid-β deposition in Alzheimer disease spectrum.

PubMed

Cho, Hanna; Lee, Hye Sun; Choi, Jae Yong; Lee, Jae Hoon; Ryu, Young Hoon; Lee, Myung Sik; Lyoo, Chul Hyoung

2018-04-17

We investigated sequential order between tau and amyloid-β (Aβ) deposition in Alzheimer disease spectrum using a conditional probability method. Two hundred twenty participants underwent 18 F-flortaucipir and 18 F-florbetaben positron emission tomography scans and neuropsychological tests. The presence of tau and Aβ in each region and impairment in each cognitive domain were determined by Z-score cutoffs. By comparing pairs of conditional probabilities, the sequential order of tau and Aβ deposition were determined. Probability for the presence of tau in the entorhinal cortex was higher than that of Aβ in all cortical regions, and in the medial temporal cortices, probability for the presence of tau was higher than that of Aβ. Conversely, in the remaining neocortex above the inferior temporal cortex, probability for the presence of Aβ was always higher than that of tau. Tau pathology in the entorhinal cortex may appear earlier than neocortical Aβ and may spread in the absence of Aβ within the neighboring medial temporal regions. However, Aβ may be required for massive tau deposition in the distant cortical areas. Copyright © 2018 Elsevier Inc. All rights reserved.

Rhinal and Dorsolateral Prefrontal Cortex Lesions Produce Selective Impairments in Object and Spatial Learning and Memory in Canines

PubMed Central

Christie, Lori-Ann; Saunders, Richard C.; Kowalska, Danuta, M.; MacKay, William A.; Head, Elizabeth; Cotman, Carl W.; Milgram, Norton W.

2014-01-01

To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed non-matching to sample, or DNMS) and a spatial (delayed non-matching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-sec delay, suggesting disrupted retention of the general task rules, however, this impairment was transient; long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a non-matching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals. PMID:18792072

Impaired Verbal Associative Learning after Resection of Left Perirhinal Cortex

ERIC Educational Resources Information Center

Weintrob, David L.; Saling, Michael M.; Berkovic, Samuel F.; Reutens, David C.

2007-01-01

Some patients considered for left temporal lobectomy for epilepsy present with normal verbal learning and no MRI evidence of hippocampal pathology. In order to preserve learning function, the surgical approach in these cases often aims at sparing the hippocampus. Parahippocampal structures, including the left perirhinal region, however, also…

Disturbed prefrontal and temporal brain function during emotion and cognition interaction in criminal psychopathy.

PubMed

Müller, Jürgen L; Sommer, Monika; Döhnel, Katrin; Weber, Tatjana; Schmidt-Wilcke, Tobias; Hajak, Göran

2008-01-01

Impaired emotional responsiveness has been revealed as a hallmark of psychopathy. In spite of an increasing database on emotion processing, studies on cognitive function and in particular on the impact of emotion on cognition in psychopathy are rare. We used pictures from the International Affective Picture Set (IAPS) and a Simon Paradigm to address emotion-cognition interaction while functional and structural imaging data were obtained in 12 healthy controls and 10 psychopaths. We found an impaired emotion-cognition interaction in psychopaths that correlated with a changed prefrontal and temporal brain activation. With regard to the temporal cortex, it is shown that structure and function of the right superior temporal gyrus is disturbed in psychopathy, supporting a neurobiological approach to psychopathy, in which structure and function of the right STG may be important. (c) 2008 John Wiley & Sons, Ltd.

Intracerebral stimulation of left and right ventral temporal cortex during object naming.

PubMed

Bédos Ulvin, Line; Jonas, Jacques; Brissart, Hélène; Colnat-Coulbois, Sophie; Thiriaux, Anne; Vignal, Jean-Pierre; Maillard, Louis

2017-12-01

While object naming is traditionally considered asa left hemisphere function, neuroimaging studies have reported activations related to naming in the ventral temporal cortex (VTC) bilaterally. Our aim was to use intracerebral electrical stimulation to specifically compare left and right VTC in naming. In twenty-three epileptic patients tested for visual object naming during stimulation, the proportion of naming impairments was significantly higher in the left than in the right VTC (31.3% vs 13.6%). The highest proportions of positive naming sites were found in the left fusiform gyrus and occipito-temporal sulcus (47.5% and 31.8%). For 17 positive left naming sites, an additional semantic picture matching was carried out, always successfully performed. Our results showed the enhanced role of the left compared to the right VTC in naming and suggest that it may be involved in lexical retrieval rather than in semantic processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Right anterior temporal lobe dysfunction underlies theory of mind impairments in semantic dementia.

PubMed

Irish, Muireann; Hodges, John R; Piguet, Olivier

2014-04-01

Semantic dementia is a progressive neurodegenerative disorder characterized by the amodal and profound loss of semantic knowledge attributable to the degeneration of the left anterior temporal lobe. Although traditionally conceptualized as a language disorder, patients with semantic dementia display significant alterations in behaviour and socioemotional functioning. Recent evidence points to an impaired capacity for theory of mind in predominantly left-lateralized cases of semantic dementia; however, it remains unclear to what extent semantic impairments contribute to these deficits. Further the neuroanatomical signature of such disturbance remains unknown. Here, we sought to determine the neural correlates of theory of mind performance in patients with left predominant semantic dementia (n=11), in contrast with disease-matched cases with behavioural-variant frontotemporal dementia (n=10) and Alzheimer's disease (n=10), and healthy older individuals (n=14) as control participants. Participants completed a simple cartoons task, in which they were required to describe physical and theory of mind scenarios. Irrespective of subscale, patients with semantic dementia exhibited marked impairments relative to control subjects; however, only theory of mind deficits persisted when we covaried for semantic comprehension. Voxel-based morphometry analyses revealed that atrophy in right anterior temporal lobe structures, including the right temporal fusiform cortex, right inferior temporal gyrus, bilateral temporal poles and amygdalae, correlated significantly with theory of mind impairments in the semantic dementia group. Our results point to the marked disruption of cognitive functions beyond the language domain in semantic dementia, not exclusively attributable to semantic processing impairments. The significant involvement of right anterior temporal structures suggests that with disease evolution, the encroachment of pathology into the contralateral hemisphere heralds the onset of social cognitive deficits in this syndrome.

Dopamine D2 receptor levels in striatum, thalamus, substantia nigra, limbic regions, and cortex in schizophrenic subjects.

PubMed

Kessler, Robert M; Woodward, Neil D; Riccardi, Patrizia; Li, Rui; Ansari, M Sib; Anderson, Sharlett; Dawant, Benoit; Zald, David; Meltzer, Herbert Y

2009-06-15

Studies in schizophrenic patients have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus, and cortex that have been related to positive symptoms and cognitive impairments. [(18)F]fallypride positron emission tomography studies were performed in off-medication or never-medicated schizophrenic subjects (n = 11, 6 men, 5 women; mean age of 30.5 +/- 8.0 [SD] years; 4 drug-naive) and age-matched healthy subjects (n = 11, 5 men, 6 women, mean age of 31.6 +/- 9.2 [SD]) to examine dopamine D(2) receptor (DA D(2)r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus. In schizophrenic subjects, increased DA D(2)r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with ROI data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex ROI (r = .94, p = .0001), which remained significant after correction for multiple comparisons (p < .03). Correlations of symptoms with parametric images of DA D(2)r levels revealed no significant clusters of correlations with negative symptoms but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum. The results of this study demonstrate abnormal DA D(2)r-mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D(2)r mediate positive symptoms.

Distortion of time interval reproduction in an epileptic patient with a focal lesion in the right anterior insular/inferior frontal cortices.

PubMed

Monfort, Vincent; Pfeuty, Micha; Klein, Madelyne; Collé, Steffie; Brissart, Hélène; Jonas, Jacques; Maillard, Louis

2014-11-01

This case report on an epileptic patient suffering from a focal lesion at the junction of the right anterior insular cortex (AIC) and the adjacent inferior frontal cortex (IFC) provides the first evidence that damage to this brain region impairs temporal performance in a visual time reproduction task in which participants had to reproduce the presentation duration (3, 5 and 7s) of emotionally-neutral and -negative pictures. Strikingly, as compared to a group of healthy subjects, the AIC/IFC case considerably overestimated reproduction times despite normal variability. The effect was obtained in all duration and emotion conditions. Such a distortion in time reproduction was not observed in four other epileptic patients without insular or inferior frontal damage. Importantly, the absolute extent of temporal over-reproduction increased in proportion to the magnitude of the target durations, which concurs with the scalar property of interval timing, and points to an impairment of time-specific rather than of non temporal (such as motor) mechanisms. Our data suggest that the disability in temporal reproduction of the AIC/IFC case would result from a distorted memory representation of the encoded duration, occurring during the process of storage and/or of recovery from memory and leading to a deviation of the temporal judgment during the reproduction task. These findings support the recent proposal that the anterior insular/inferior frontal cortices would be involved in time interval representation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Consolidation of visual associative long-term memory in the temporal cortex of primates.

PubMed

Miyashita, Y; Kameyama, M; Hasegawa, I; Fukushima, T

1998-01-01

Neuropsychological theories have proposed a critical role for the interaction between the medial temporal lobe and the neocortex in the formation of long-term memory for facts and events, which has often been tested by learning of a series of paired words or figures in humans. We have examined neural mechanisms underlying the memory "consolidation" process by single-unit recording and molecular biological methods in an animal model of a visual pair-association task in monkeys. In our previous studies, we found that long-term associative representations of visual objects are acquired through learning in the neural network of the anterior inferior temporal (IT) cortex. In this article, we propose the hypothesis that limbic neurons undergo rapid modification of synaptic connectivity and provide backward signals that guide the reorganization of neocortical neural circuits. Two experiments tested this hypothesis: (1) we examined the role of the backward connections from the medial temporal lobe to the IT cortex by injecting ibotenic acid into the entorhinal and perirhinal cortices, which provided massive backward projections ipsilaterally to the IT cortex. We found that the limbic lesion disrupted the associative code of the IT neurons between the paired associates, without impairing the visual response to each stimulus. (2) We then tested the first half of this hypothesis by detecting the expression of immediate-early genes in the monkey temporal cortex. We found specific expression of zif268 during the learning of a new set of paired associates in the pair-association task, most intensively in area 36 of the perirhinal cortex. All these results with the visual pair-association task support our hypothesis and demonstrate that the consolidation process, which was first proposed on the basis of clinico-psychological evidence, can now be examined in primates using neurophysiolocical and molecular biological approaches. Copyright 1998 Academic Press.

Neural correlates of prospective memory impairments in schizophrenia.

PubMed

Chen, Xing-jie; Wang, Ya; Wang, Yi; Yang, Tian-xiao; Zou, Lai-quan; Huang, Jia; Li, Feng-hua; Chen, An-tao; Wang, Wei-hong; Zheng, Han-feng; Cheung, Eric F C; Shum, David H K; Chan, Raymond C K

2016-02-01

Prospective memory (PM) refers to the ability to remember to carry out intended actions after a delay. PM impairments are common in schizophrenia patients and are thought to be related to their prefrontal cortex dysfunction; however, this has not yet been examined directly in the research literature. The current study aimed to examine abnormalities in brain activation during PM task performance in schizophrenia patients. Twenty-two schizophrenia patients and 25 matched healthy controls were scanned in a 3-T MRI machine while performing a PM task. The results showed that compared to the healthy controls, schizophrenia patients performed significantly worse on the PM task. Furthermore, they exhibited decreased brain activation in frontal cortex including the right superior frontal gyri (Brodmann area 10), and other related brain areas like the anterior cingulate gyrus, parietal and temporal cortex, including precuneus, and some subcortext, including parahippocampal gyrus and putamen. These findings confirm the involvement and importance of the prefrontal cortex in PM and show evidence of hypofrontality in schizophrenia patients while performing a PM task. PsycINFO Database Record (c) 2016 APA, all rights reserved.

Monkey’s short-term auditory memory nearly abolished by combined removal of the rostral superior temporal gyrus and rhinal cortices

PubMed Central

Fritz, Jonathan B.; Malloy, Megan; Mishkin, Mortimer; Saunders, Richard C.

2016-01-01

While monkeys easily acquire the rules for performing visual and tactile delayed matching-to-sample, a method for testing recognition memory, they have extraordinary difficulty acquiring a similar rule in audition. Another striking difference between the modalities is that whereas bilateral ablation of the rhinal cortex (RhC) leads to profound impairment in visual and tactile recognition, the same lesion has no detectable effect on auditory recognition memory (Fritz et al., 2005). In our previous study, a mild impairment in auditory memory was obtained following bilateral ablation of the entire medial temporal lobe (MTL), including the RhC, and an equally mild effect was observed after bilateral ablation of the auditory cortical areas in the rostral superior temporal gyrus (rSTG). In order to test the hypothesis that each of these mild impairments was due to partial disconnection of acoustic input to a common target (e.g., the ventromedial prefrontal cortex), in the current study we examined the effects of a more complete auditory disconnection of this common target by combining the removals of both the rSTG and the MTL. We found that the combined lesion led to forgetting thresholds (performance at 75% accuracy) that fell precipitously from the normal retention duration of ~30–40 seconds to a duration of ~1–2 seconds, thus nearly abolishing auditory recognition memory, and leaving behind only a residual echoic memory. PMID:26707975

Pure word deafness following left temporal damage: Behavioral and neuroanatomical evidence from a new case.

PubMed

Maffei, Chiara; Capasso, Rita; Cazzolli, Giulia; Colosimo, Cesare; Dell'Acqua, Flavio; Piludu, Francesca; Catani, Marco; Miceli, Gabriele

2017-12-01

Pure Word Deafness (PWD) is a rare disorder, characterized by selective loss of speech input processing. Its most common cause is temporal damage to the primary auditory cortex of both hemispheres, but it has been reported also following unilateral lesions. In unilateral cases, PWD has been attributed to the disconnection of Wernicke's area from both right and left primary auditory cortex. Here we report behavioral and neuroimaging evidence from a new case of left unilateral PWD with both cortical and white matter damage due to a relatively small stroke lesion in the left temporal gyrus. Selective impairment in auditory language processing was accompanied by intact processing of nonspeech sounds and normal speech, reading and writing. Performance on dichotic listening was characterized by a reversal of the right-ear advantage typically observed in healthy subjects. Cortical thickness and gyral volume were severely reduced in the left superior temporal gyrus (STG), although abnormalities were not uniformly distributed and residual intact cortical areas were detected, for example in the medial portion of the Heschl's gyrus. Diffusion tractography documented partial damage to the acoustic radiations (AR), callosal temporal connections and intralobar tracts dedicated to single words comprehension. Behavioral and neuroimaging results in this case are difficult to integrate in a pure cortical or disconnection framework, as damage to primary auditory cortex in the left STG was only partial and Wernicke's area was not completely isolated from left or right-hemisphere input. On the basis of our findings we suggest that in this case of PWD, concurrent partial topological (cortical) and disconnection mechanisms have contributed to a selective impairment of speech sounds. The discrepancy between speech and non-speech sounds suggests selective damage to a language-specific left lateralized network involved in phoneme processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory.

PubMed

Goyal, Abhinav; Miller, Jonathan; Watrous, Andrew J; Lee, Sang Ah; Coffey, Tom; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn A; Inman, Cory; Sheth, Sameer A; Wanda, Paul A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Jacobs, Joshua

2018-05-09

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory. Copyright © 2018 the authors 0270-6474/18/384471-11$15.00/0.

Reduction of Interhemispheric Functional Brain Connectivity in Early Blindness: A Resting-State fMRI Study

PubMed Central

2017-01-01

Objective The purpose of this study was to investigate the resting-state interhemispheric functional connectivity in early blindness by using voxel-mirrored homotopic connectivity (VMHC). Materials and Methods Sixteen early blind patients (EB group) and sixteen age- and gender-matched sighted control volunteers (SC group) were recruited in this study. We used VMHC to identify brain areas with significant differences in functional connectivity between different groups and used voxel-based morphometry (VBM) to calculate the individual gray matter volume (GMV). Results VMHC analysis showed a significantly lower connectivity in primary visual cortex, visual association cortex, and somatosensory association cortex in EB group compared to sighted controls. Additionally, VBM analysis revealed that GMV was reduced in the left lateral calcarine cortices in EB group compared to sighted controls, while it was increased in the left lateral middle occipital gyri. Statistical analysis showed the duration of blindness negatively correlated with VMHC in the bilateral middle frontal gyri, middle temporal gyri, and inferior temporal gyri. Conclusions Our findings help elucidate the pathophysiological mechanisms of EB. The interhemispheric functional connectivity was impaired in EB patients. Additionally, the middle frontal gyri, middle temporal gyri, and inferior temporal gyri may be potential target regions for rehabilitation. PMID:28656145

Functional connectivity of parietal cortex during temporal selective attention.

PubMed

Tyler, Sarah C; Dasgupta, Samhita; Agosta, Sara; Battelli, Lorella; Grossman, Emily D

2015-04-01

Perception of natural experiences requires allocation of attention towards features, objects, and events that are moving and changing over time. This allocation of attention is controlled by large-scale brain networks that, when damaged, cause widespread cognitive deficits. In particular, damage to ventral parietal cortex (right lateralized TPJ, STS, supramarginal and angular gyri) is associated with failures to selectively attend to and isolate features embedded within rapidly changing visual sequences (Battelli, Pascual-Leone, & Cavanagh, 2007; Husain, Shapiro, Martin, & Kennard, 1997). In this study, we used fMRI to investigate the neural activity and functional connectivity of intact parietal cortex while typical subjects judged the relative onsets and offsets of rapidly flickering tokens (a phase discrimination task in which right parietal patients are impaired). We found two regions in parietal cortex correlated with task performance: a bilateral posterior TPJ (pTPJ) and an anterior right-lateralized TPJ (R aTPJ). Both regions were deactivated when subjects engaged in the task but showed different patterns of functional connectivity. The bilateral pTPJ was strongly connected to nodes within the default mode network (DMN) and the R aTPJ was connected to the attention network. Accurate phase discriminations were associated with increased functional correlations between sensory cortex (hMT+) and the bilateral pTPJ, whereas accuracy on a control task was associated with yoked activity in the hMT+ and the R aTPJ. We conclude that temporal selective attention is particularly sensitive for revealing information pathways between sensory and core cognitive control networks that, when damaged, can lead to nonspatial attention impairments in right parietal stroke patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automated Volumetry and Regional Thickness Analysis of Hippocampal Subfields and Medial Temporal Cortical Structures in Mild Cognitive Impairment

PubMed Central

Yushkevich, Paul A.; Pluta, John B.; Wang, Hongzhi; Xie, Long; Ding, Song-Lin; Gertje, E. C.; Mancuso, Lauren; Kliot, Daria; Das, Sandhitsu R.; Wolk, David A.

2014-01-01

We evaluate a fully automatic technique for labeling hippocampal subfields and cortical subregions in the medial temporal lobe (MTL) in in vivo 3 Tesla MRI. The method performs segmentation on a T2-weighted MRI scan with 0.4 × 0.4 × 2.0 mm3 resolution, partial brain coverage, and oblique orientation. Hippocampal subfields, entorhinal cortex, and perirhinal cortex are labeled using a pipeline that combines multi-atlas label fusion and learning-based error correction. In contrast to earlier work on automatic subfield segmentation in T2-weighted MRI (Yushkevich et al., 2010), our approach requires no manual initialization, labels hippocampal subfields over a greater anterior-posterior extent, and labels the perirhinal cortex, which is further subdivided into Brodmann areas 35 and 36. The accuracy of the automatic segmentation relative to manual segmentation is measured using cross-validation in 29 subjects from a study of amnestic Mild Cognitive Impairment (aMCI), and is highest for the dentate gyrus (Dice coefficient is 0.823), CA1 (0.803), perirhinal cortex (0.797) and entorhinal cortex (0.786) labels. A larger cohort of 83 subjects is used to examine the effects of aMCI in the hippocampal region using both subfield volume and regional subfield thickness maps. Most significant differences between aMCI and healthy aging are observed bilaterally in the CA1 subfield and in the left Brodmann area 35. Thickness analysis results are consistent with volumetry, but provide additional regional specificity and suggest non-uniformity in the effects of aMCI on hippocampal subfields and MTL cortical subregions. PMID:25181316

Chronic intermittent hypoxia induces changes on the expression and activity of neprilysin (EC 3.4.24.11) in the brain of rats.

PubMed

de Oliveira, Renato W; Julian, Guilherme S; Perry, Juliana C; Tufik, Sergio; Chagas, Jair R

2018-06-21

Obstructive sleep apnea (OSA) is a frequent sleeping breathing disorder associated with cognitive impairments. Neprilysin (NEP) is responsible for degrading several substrates related to cognition; however, the effect of chronic intermittent hypoxia (CIH) on NEP is still unknown. This study aimed to evaluate the expression and activity of NEP in cognitive-related brain structures of rats submitted to CIH. Western blot, qRT-PCR and enzyme activity assay, demonstrated that a six-week intermittent hypoxia increased NEP expression and activity, selectively in temporal cortex, but not in the hippocampus and frontal cortex. The increase in NEP activity and expression was reverted followed by two weeks recovery in normoxia. These data show that CIH protocol increases the expression and activity of NEP selectively in the temporal cortex. Additional mechanisms must be investigated to elucidate the effects of CIH in cognition. Copyright © 2018 Elsevier B.V. All rights reserved.

Dopamine D2 Receptor Levels in Striatum, Thalamus, Substantia Nigra, Limbic Regions, and Cortex in Schizophrenic Subjects

PubMed Central

Kessler, Robert M; Woodward, Neil D; Riccardi, Patrizia; Li, Rui; Ansari, M Sib; Anderson, Sharlett; Dawant, Benoit; Zald, David; Meltzer, Herbert Y

2009-01-01

Background Studies in schizophrenics have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus and cortex which have been related to positive symptoms and cognitive impairments. Methods [18F]fallypride PET studies were performed in off medication or never medicated schizophrenic subjects [N = 11, 6 M, 5 F; mean age of 30.5 ± 8.0 (S.D.); 4 drug naive] and age matched healthy subjects [N = 11, 5M, 6F, mean age of 31.6 ± 9.2 (S.D.)] to examine dopamine D2 receptor (DA D2r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus. Results In schizophrenic subjects increased DA D2r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with region of interest data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex region of interest (r = 0.94, P = 0.0001) which remained significant after correction for multiple comparisons (P<0.03). Correlations of symptoms with parametric images of DA D2r levels revealed no significant clusters of correlations with negative symptoms, but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum. Conclusions The results of this study demonstrate abnormal DA D2r mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D2r mediate positive symptoms. PMID:19251247

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.

Distinct cortical correlates of autistic versus antisocial traits in a longitudinal sample of typically developing youth

PubMed Central

Wallace, Gregory L.; Shaw, Philip; Lee, Nancy Raitano; Clasen, Liv S.; Raznahan, Armin; Lenroot, Rhoshel K.; Martin, Alex; Giedd, Jay N.

2012-01-01

In humans, behaviors associated with autism and antisociality, disorders characterized by distinct social impairments, can be viewed as quantitative traits that range from frank impairment to normal variation, as found in the general population. Neuroimaging investigations of autism and antisociality demonstrate diagnostically specific aberrant cortical brain structure. However, little is known about structural brain correlates of social behavior in non-clinical populations. Therefore, we sought to determine if autistic and antisocial traits exhibit dissociable cortical correlates and whether these associations are stable across development among typically developing youth. 323 typically developing youth (age at first scan: mean=10.63, SD=3.71 years) underwent anatomic magnetic resonance imaging (1–6 scans each; total=742 scans), and provided ratings of autistic and antisocial traits. Higher autistic trait ratings were associated with thinner cortex most prominently in right superior temporal sulcus while higher antisocial trait ratings were associated with thinner cortex in primarily bilateral anterior prefrontal cortices. There was no interaction with age, indicating that these brain-behavior associations were stable across development. Using assessments of both subclinical autistic and subclinical antisocial traits within a large longitudinal sample of typically developing youth, we demonstrate dissociable neuroanatomic correlations that parallel those found in the frank clinical disorders of autism (e.g., superior temporal cortex) and antisociality (e.g., anterior prefrontal cortex). Moreover, these correlations appear to be established in early childhood and remain fixed into early adulthood. These results support the dimensional view of psychopathology and provide neural signatures that can serve as informative endophenotypes for future genetic studies. PMID:22492041

Distinct cortical correlates of autistic versus antisocial traits in a longitudinal sample of typically developing youth.

PubMed

Wallace, Gregory L; Shaw, Philip; Lee, Nancy Raitano; Clasen, Liv S; Raznahan, Armin; Lenroot, Rhoshel K; Martin, Alex; Giedd, Jay N

2012-04-04

In humans, behaviors associated with autism and antisociality, disorders characterized by distinct social impairments, can be viewed as quantitative traits that range from frank impairment to normal variation, as found in the general population. Neuroimaging investigations of autism and antisociality demonstrate diagnostically specific aberrant cortical brain structure. However, little is known about structural brain correlates of social behavior in nonclinical populations. Therefore, we sought to determine whether autistic and antisocial traits exhibit dissociable cortical correlates and whether these associations are stable across development among typically developing youth. Three hundred twenty-three typically developing youth (age at first scan: mean = 10.63, SD = 3.71 years) underwent anatomic magnetic resonance imaging (1-6 scans each; total = 742 scans), and provided ratings of autistic and antisocial traits. Higher autistic trait ratings were associated with thinner cortex most prominently in right superior temporal sulcus while higher antisocial trait ratings were associated with thinner cortex in primarily bilateral anterior prefrontal cortices. There was no interaction with age, indicating that these brain-behavior associations were stable across development. Using assessments of both subclinical autistic and subclinical antisocial traits within a large longitudinal sample of typically developing youth, we demonstrate dissociable neuroanatomic correlations that parallel those found in the frank clinical disorders of autism (e.g., superior temporal cortex) and antisociality (e.g., anterior prefrontal cortex). Moreover, these correlations appear to be established in early childhood and remain fixed into early adulthood. These results support the dimensional view of psychopathology and provide neural signatures that can serve as informative endophenotypes for future genetic studies.

Default mode network in childhood autism: posteromedial cortex heterogeneity and relationship with social deficits.

PubMed

Lynch, Charles J; Uddin, Lucina Q; Supekar, Kaustubh; Khouzam, Amirah; Phillips, Jennifer; Menon, Vinod

2013-08-01

The default mode network (DMN), a brain system anchored in the posteromedial cortex, has been identified as underconnected in adults with autism spectrum disorder (ASD). However, to date there have been no attempts to characterize this network and its involvement in mediating social deficits in children with ASD. Furthermore, the functionally heterogeneous profile of the posteromedial cortex raises questions regarding how altered connectivity manifests in specific functional modules within this brain region in children with ASD. Resting-state functional magnetic resonance imaging and an anatomically informed approach were used to investigate the functional connectivity of the DMN in 20 children with ASD and 19 age-, gender-, and IQ-matched typically developing (TD) children. Multivariate regression analyses were used to test whether altered patterns of connectivity are predictive of social impairment severity. Compared with TD children, children with ASD demonstrated hyperconnectivity of the posterior cingulate and retrosplenial cortices with predominately medial and anterolateral temporal cortex. In contrast, the precuneus in ASD children demonstrated hypoconnectivity with visual cortex, basal ganglia, and locally within the posteromedial cortex. Aberrant posterior cingulate cortex hyperconnectivity was linked with severity of social impairments in ASD, whereas precuneus hypoconnectivity was unrelated to social deficits. Consistent with previous work in healthy adults, a functionally heterogeneous profile of connectivity within the posteromedial cortex in both TD and ASD children was observed. This work links hyperconnectivity of DMN-related circuits to the core social deficits in young children with ASD and highlights fundamental aspects of posteromedial cortex heterogeneity. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Reduced Cortical Thickness and Increased Surface Area in Antisocial Personality Disorder

PubMed Central

Jiang, Weixiong; Li, Gang; Liu, Huasheng; Shi, Feng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

2016-01-01

Antisocial Personality Disorder (ASPD), one of whose characteristics is high impulsivity, is of great interest in the field of brain structure and function. However, little is known about possible impairments in the cortical anatomy in ASPD, in terms of cortical thickness and surface area, as well as their possible relationship with impulsivity. In this neuroimaging study, we first investigated the changes of cortical thickness and surface area in ASPD patients, in comparison to those of healthy controls, and then performed correlation analyses between these measures and the ability of impulse control. We found that ASPD patients showed thinner cortex while larger surface area in several specific brain regions, i.e., bilateral superior frontal gyrus, orbitofrontal and triangularis, insula cortex, precuneus, middle frontal gyrus, middle temporal gyrus, and left bank of superior temporal sulcus. In addition, we also found that the ability of impulse control was positively correlated with cortical thickness in the superior frontal gyrus, middle frontal gyrus, orbitofrontal cortex, pars triangularis, superior temporal gyrus, and insula cortex. To our knowledge, this study is the first to reveal simultaneous changes in cortical thickness and surface area in ASPD, as well as their relationship with impulsivity. These cortical structural changes may introduce uncontrolled and callous behavioral characteristic in ASPD patients, and these potential biomarkers may be very helpful in understanding the pathomechanism of ASPD. PMID:27600947

Reduced cortical thickness and increased surface area in antisocial personality disorder.

PubMed

Jiang, Weixiong; Li, Gang; Liu, Huasheng; Shi, Feng; Wang, Tao; Shen, Celina; Shen, Hui; Lee, Seong-Whan; Hu, Dewen; Wang, Wei; Shen, Dinggang

2016-11-19

Antisocial personality disorder (ASPD), one of whose characteristics is high impulsivity, is of great interest in the field of brain structure and function. However, little is known about possible impairments in the cortical anatomy in ASPD, in terms of cortical thickness (CTh) and surface area (SA), as well as their possible relationship with impulsivity. In this neuroimaging study, we first investigated the changes of CTh and SA in ASPD patients, in comparison to those of healthy controls, and then performed correlation analyses between these measures and the ability of impulse control. We found that ASPD patients showed thinner cortex while larger SA in several specific brain regions, i.e., bilateral superior frontal gyrus (SFG), orbitofrontal and triangularis, insula cortex, precuneus, middle frontal gyrus (MFG), middle temporal gyrus (MTG), and left bank of superior temporal sulcus (STS). In addition, we also found that the ability of impulse control was positively correlated with CTh in the SFG, MFG, orbitofrontal cortex (OFC), pars triangularis, superior temporal gyrus (STG), and insula cortex. To our knowledge, this study is the first to reveal simultaneous changes in CTh and SA in ASPD, as well as their relationship with impulsivity. These cortical structural changes may introduce uncontrolled and callous behavioral characteristic in ASPD patients, and these potential biomarkers may be very helpful in understanding the pathomechanism of ASPD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neonatal Perirhinal Lesions in Rhesus Macaques Alter Performance on Working Memory Tasks with High Proactive Interference.

PubMed

Weiss, Alison R; Nadji, Ryhan; Bachevalier, Jocelyne

2015-01-01

The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM. Within the medial temporal lobe (MTL) structures, the perirhinal cortex, which has extensive direct interactions with the lateral and orbital prefrontal cortex, is required to form active/flexible representations of familiar objects. However, its participation in WM processes has not be fully explored. The goal of this study was to assess the effects of neonatal perirhinal lesions on maintenance and monitoring WM processes. As adults, animals with neonatal perirhinal lesions and their matched controls were tested in three object-based (non-spatial) WM tasks that tapped different WM processing domains, e.g., maintenance only (Session-unique Delayed-nonmatching-to Sample, SU-DNMS), and maintenance and monitoring (Object-Self-Order, OBJ-SO; Serial Order Memory Task, SOMT). Neonatal perirhinal lesions transiently impaired the acquisition of SU-DNMS at a short (5 s) delay, but not when re-tested with a longer delay (30 s). The same neonatal lesions severely impacted acquisition of OBJ-SO task, and the impairment was characterized by a sharp increase in perseverative errors. By contrast, neonatal perirhinal lesion spared the ability to monitor the temporal order of items in WM as measured by the SOMT. Contrary to the SU-DNMS and OBJ-SO, which re-use the same stimuli across trials and thus produce proactive interference, the SOMT uses novel objects on each trial and is devoid of interference. Therefore, the impairment of monkeys with neonatal perirhinal lesions on SU-DNMS and OBJ-SO tasks is likely to be caused by an inability to solve working memory tasks with high proactive interference. The sparing of performance on the SOMT demonstrates that neonatal perirhinal lesions do not alter working memory processes per se but rather impact processes modulating impulse control and/or behavioral flexibility.

Atypical right hemisphere response to slow temporal modulations in children with developmental dyslexia.

PubMed

Cutini, Simone; Szűcs, Dénes; Mead, Natasha; Huss, Martina; Goswami, Usha

2016-12-01

Phase entrainment of neuronal oscillations is thought to play a central role in encoding speech. Children with developmental dyslexia show impaired phonological processing of speech, proposed theoretically to be related to atypical phase entrainment to slower temporal modulations in speech (<10Hz). While studies of children with dyslexia have found atypical phase entrainment in the delta band (~2Hz), some studies of adults with developmental dyslexia have shown impaired entrainment in the low gamma band (~35-50Hz). Meanwhile, studies of neurotypical adults suggest asymmetric temporal sensitivity in auditory cortex, with preferential processing of slower modulations by right auditory cortex, and faster modulations processed bilaterally. Here we compared neural entrainment to slow (2Hz) versus faster (40Hz) amplitude-modulated noise using fNIRS to study possible hemispheric asymmetry effects in children with developmental dyslexia. We predicted atypical right hemisphere responding to 2Hz modulations for the children with dyslexia in comparison to control children, but equivalent responding to 40Hz modulations in both hemispheres. Analyses of HbO concentration revealed a right-lateralised region focused on the supra-marginal gyrus that was more active in children with dyslexia than in control children for 2Hz stimulation. We discuss possible links to linguistic prosodic processing, and interpret the data with respect to a neural 'temporal sampling' framework for conceptualizing the phonological deficits that characterise children with developmental dyslexia across languages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Anterior temporal cortex and semantic memory: reconciling findings from neuropsychology and functional imaging.

PubMed

Rogers, Timothy T; Hocking, Julia; Noppeney, Uta; Mechelli, Andrea; Gorno-Tempini, Maria Luisa; Patterson, Karalyn; Price, Cathy J

2006-09-01

Studies of semantic impairment arising from brain disease suggest that the anterior temporal lobes are critical for semantic abilities in humans; yet activation of these regions is rarely reported in functional imaging studies of healthy controls performing semantic tasks. Here, we combined neuropsychological and PET functional imaging data to show that when healthy subjects identify concepts at a specific level, the regions activated correspond to the site of maximal atrophy in patients with relatively pure semantic impairment. The stimuli were color photographs of common animals or vehicles, and the task was category verification at specific (e.g., robin), intermediate (e.g., bird), or general (e.g., animal) levels. Specific, relative to general, categorization activated the antero-lateral temporal cortices bilaterally, despite matching of these experimental conditions for difficulty. Critically, in patients with atrophy in precisely these areas, the most pronounced deficit was in the retrieval of specific semantic information.

Voice Recognition in Face-Blind Patients

PubMed Central

Liu, Ran R.; Pancaroglu, Raika; Hills, Charlotte S.; Duchaine, Brad; Barton, Jason J. S.

2016-01-01

Right or bilateral anterior temporal damage can impair face recognition, but whether this is an associative variant of prosopagnosia or part of a multimodal disorder of person recognition is an unsettled question, with implications for cognitive and neuroanatomic models of person recognition. We assessed voice perception and short-term recognition of recently heard voices in 10 subjects with impaired face recognition acquired after cerebral lesions. All 4 subjects with apperceptive prosopagnosia due to lesions limited to fusiform cortex had intact voice discrimination and recognition. One subject with bilateral fusiform and anterior temporal lesions had a combined apperceptive prosopagnosia and apperceptive phonagnosia, the first such described case. Deficits indicating a multimodal syndrome of person recognition were found only in 2 subjects with bilateral anterior temporal lesions. All 3 subjects with right anterior temporal lesions had normal voice perception and recognition, 2 of whom performed normally on perceptual discrimination of faces. This confirms that such lesions can cause a modality-specific associative prosopagnosia. PMID:25349193

Monkey׳s short-term auditory memory nearly abolished by combined removal of the rostral superior temporal gyrus and rhinal cortices.

PubMed

Fritz, Jonathan B; Malloy, Megan; Mishkin, Mortimer; Saunders, Richard C

2016-06-01

While monkeys easily acquire the rules for performing visual and tactile delayed matching-to-sample, a method for testing recognition memory, they have extraordinary difficulty acquiring a similar rule in audition. Another striking difference between the modalities is that whereas bilateral ablation of the rhinal cortex (RhC) leads to profound impairment in visual and tactile recognition, the same lesion has no detectable effect on auditory recognition memory (Fritz et al., 2005). In our previous study, a mild impairment in auditory memory was obtained following bilateral ablation of the entire medial temporal lobe (MTL), including the RhC, and an equally mild effect was observed after bilateral ablation of the auditory cortical areas in the rostral superior temporal gyrus (rSTG). In order to test the hypothesis that each of these mild impairments was due to partial disconnection of acoustic input to a common target (e.g., the ventromedial prefrontal cortex), in the current study we examined the effects of a more complete auditory disconnection of this common target by combining the removals of both the rSTG and the MTL. We found that the combined lesion led to forgetting thresholds (performance at 75% accuracy) that fell precipitously from the normal retention duration of ~30 to 40s to a duration of ~1 to 2s, thus nearly abolishing auditory recognition memory, and leaving behind only a residual echoic memory. This article is part of a Special Issue entitled SI: Auditory working memory. Published by Elsevier B.V.

Local but not long-range microstructural differences of the ventral temporal cortex in developmental prosopagnosia

PubMed Central

Song, Sunbin; Garrido, Lúcia; Nagy, Zoltan; Mohammadi, Siawoosh; Steel, Adam; Driver, Jon; Dolan, Ray J.; Duchaine, Bradley; Furl, Nicholas

2015-01-01

Individuals with developmental prosopagnosia (DP) experience face recognition impairments despite normal intellect and low-level vision and no history of brain damage. Prior studies using diffusion tensor imaging in small samples of subjects with DP (n=6 or n=8) offer conflicting views on the neurobiological bases for DP, with one suggesting white matter differences in two major long-range tracts running through the temporal cortex, and another suggesting white matter differences confined to fibers local to ventral temporal face-specific functional regions of interest (fROIs) in the fusiform gyrus. Here, we address these inconsistent findings using a comprehensive set of analyzes in a sample of DP subjects larger than both prior studies combined (n=16). While we found no microstructural differences in long-range tracts between DP and age-matched control participants, we found differences local to face-specific fROIs, and relationships between these microstructural measures with face recognition ability. We conclude that subtle differences in local rather than long-range tracts in the ventral temporal lobe are more likely associated with developmental prosopagnosia. PMID:26456436

Neural Substrates of Auditory Emotion Recognition Deficits in Schizophrenia.

PubMed

Kantrowitz, Joshua T; Hoptman, Matthew J; Leitman, David I; Moreno-Ortega, Marta; Lehrfeld, Jonathan M; Dias, Elisa; Sehatpour, Pejman; Laukka, Petri; Silipo, Gail; Javitt, Daniel C

2015-11-04

Deficits in auditory emotion recognition (AER) are a core feature of schizophrenia and a key component of social cognitive impairment. AER deficits are tied behaviorally to impaired ability to interpret tonal ("prosodic") features of speech that normally convey emotion, such as modulations in base pitch (F0M) and pitch variability (F0SD). These modulations can be recreated using synthetic frequency modulated (FM) tones that mimic the prosodic contours of specific emotional stimuli. The present study investigates neural mechanisms underlying impaired AER using a combined event-related potential/resting-state functional connectivity (rsfMRI) approach in 84 schizophrenia/schizoaffective disorder patients and 66 healthy comparison subjects. Mismatch negativity (MMN) to FM tones was assessed in 43 patients/36 controls. rsfMRI between auditory cortex and medial temporal (insula) regions was assessed in 55 patients/51 controls. The relationship between AER, MMN to FM tones, and rsfMRI was assessed in the subset who performed all assessments (14 patients, 21 controls). As predicted, patients showed robust reductions in MMN across FM stimulus type (p = 0.005), particularly to modulations in F0M, along with impairments in AER and FM tone discrimination. MMN source analysis indicated dipoles in both auditory cortex and anterior insula, whereas rsfMRI analyses showed reduced auditory-insula connectivity. MMN to FM tones and functional connectivity together accounted for ∼50% of the variance in AER performance across individuals. These findings demonstrate that impaired preattentive processing of tonal information and reduced auditory-insula connectivity are critical determinants of social cognitive dysfunction in schizophrenia, and thus represent key targets for future research and clinical intervention. Schizophrenia patients show deficits in the ability to infer emotion based upon tone of voice [auditory emotion recognition (AER)] that drive impairments in social cognition and global functional outcome. This study evaluated neural substrates of impaired AER in schizophrenia using a combined event-related potential/resting-state fMRI approach. Patients showed impaired mismatch negativity response to emotionally relevant frequency modulated tones along with impaired functional connectivity between auditory and medial temporal (anterior insula) cortex. These deficits contributed in parallel to impaired AER and accounted for ∼50% of variance in AER performance. Overall, these findings demonstrate the importance of both auditory-level dysfunction and impaired auditory/insula connectivity in the pathophysiology of social cognitive dysfunction in schizophrenia. Copyright © 2015 the authors 0270-6474/15/3514910-13$15.00/0.

Combination of volume and perfusion parameters reveals different types of grey matter changes in schizophrenia.

PubMed

Xu, Lixue; Qin, Wen; Zhuo, Chuanjun; Liu, Huaigui; Zhu, Jiajia; Yu, Chunshui

2017-03-27

Diverse brain structural and functional changes have been reported in schizophrenia. Identifying different types of brain changes may help to understand the neural mechanisms and to develop reliable biomarkers in schizophrenia. We aimed to categorize different grey matter changes in schizophrenia based on grey matter volume (GMV) and cerebral blood flow (CBF). Structural and perfusion magnetic resonance imaging data were acquired in 100 schizophrenia patients and 95 healthy comparison subjects. Voxel-based GMV comparison was used to show structural changes, CBF analysis was used to demonstrate functional changes. We identified three types of grey matter changes in schizophrenia: structural and functional impairments in the anterior cingulate cortex and insular cortex, displaying reduction in both GMV and CBF; structural impairment with preserved function in the frontal and temporal cortices, demonstrating decreased GMV with normal CBF; pure functional abnormality in the anterior cingulate cortex and lateral prefrontal cortex and putamen, showing altered CBF with normal GMV. By combination of GMV and CBF, we identified three types of grey matter changes in schizophrenia. These findings may help to understand the complex manifestations and to develop reliable biomarkers in schizophrenia.

Abnormalities of Intrinsic Functional Connectivity in Autism Spectrum Disorders

PubMed Central

Monk, Christopher S.; Peltier, Scott J.; Wiggins, Jillian Lee; Weng, Shih-Jen; Carrasco, Melisa; Risi, Susan; Lord, Catherine

2009-01-01

Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms. PMID:19409498

Parkinson's disease with mild cognitive impairment: severe cortical thinning antedates dementia.

PubMed

Gasca-Salas, Carmen; García-Lorenzo, Daniel; Garcia-Garcia, David; Clavero, Pedro; Obeso, José A; Lehericy, Stephane; Rodríguez-Oroz, María C

2017-07-14

Mild cognitive impairment (MCI) in Parkinson's disease (PD) is a risk factor for dementia and thus, it is of interest to elucidate if specific patterns of atrophy in PD-MCI patients are associated with a higher risk of developing dementia. We aim to define pattern(s) of regional atrophy in PD-MCI patients who developed dementia during 31 months of follow-up using cortical thickness analysis Twenty-three PD-MCI patients and 18 controls underwent brain MRI and completed a neuropsychological examination at baseline, PD-MCI patients were followed after a 31 month follow-up in order to assess their progression to dementia. At follow up, 8 PD-MCI patients had converted to dementia (PD-MCI converters) whereas 15 remained as PD-MCI (PD-MCI non-converters). All patients were at least 60 years old and suffered PD ≥ 10 years. There were no baseline differences between the two groups of patients in clinical and neuropsychological variables. The cortex of PD-MCI converters was thinner than that of PD-MCI non-converters, bilaterally in the frontal, insula and the left middle temporal areas, also displaying a more widespread pattern of cortical thinning relative to the controls. This study shows that aged and long-term PD patients with MCI who convert to dementia in the short-mid term suffer a thinning of the cortex in several areas (frontal cortex, and middle temporal lobe and insula), even when their cognitive impairment was similar to that of PD-MCI non-converters. Thus, MRI analysis of cortical thickness may represent a useful measure to identify PD-MCI patients at a higher risk of developing dementia.

Treatment for Alexia With Agraphia Following Left Ventral Occipito-Temporal Damage: Strengthening Orthographic Representations Common to Reading and Spelling

PubMed Central

Rising, Kindle; Rapcsak, Steven Z.; Beeson, Pélagie M.

2015-01-01

Purpose Damage to left ventral occipito-temporal cortex can give rise to written language impairment characterized by pure alexia/letter-by-letter (LBL) reading, as well as surface alexia and agraphia. The purpose of this study was to examine the therapeutic effects of a combined treatment approach to address concurrent LBL reading with surface alexia/agraphia. Method Simultaneous treatment to address slow reading and errorful spelling was administered to 3 individuals with reading and spelling impairments after left ventral occipito-temporal damage due to posterior cerebral artery stroke. Single-word reading/spelling accuracy, reading latencies, and text reading were monitored as outcome measures for the combined effects of multiple oral re-reading treatment and interactive spelling treatment. Results After treatment, participants demonstrated faster and more accurate single-word reading and improved text-reading rates. Spelling accuracy also improved, particularly for untrained irregular words, demonstrating generalization of the trained interactive spelling strategy. Conclusion This case series characterizes concomitant LBL with surface alexia/agraphia and demonstrates a successful treatment approach to address both the reading and spelling impairment. PMID:26110814

Treatment for Alexia With Agraphia Following Left Ventral Occipito-Temporal Damage: Strengthening Orthographic Representations Common to Reading and Spelling.

PubMed

Kim, Esther S; Rising, Kindle; Rapcsak, Steven Z; Beeson, Pélagie M

2015-10-01

Damage to left ventral occipito-temporal cortex can give rise to written language impairment characterized by pure alexia/letter-by-letter (LBL) reading, as well as surface alexia and agraphia. The purpose of this study was to examine the therapeutic effects of a combined treatment approach to address concurrent LBL reading with surface alexia/agraphia. Simultaneous treatment to address slow reading and errorful spelling was administered to 3 individuals with reading and spelling impairments after left ventral occipito-temporal damage due to posterior cerebral artery stroke. Single-word reading/spelling accuracy, reading latencies, and text reading were monitored as outcome measures for the combined effects of multiple oral re-reading treatment and interactive spelling treatment. After treatment, participants demonstrated faster and more accurate single-word reading and improved text-reading rates. Spelling accuracy also improved, particularly for untrained irregular words, demonstrating generalization of the trained interactive spelling strategy. This case series characterizes concomitant LBL with surface alexia/agraphia and demonstrates a successful treatment approach to address both the reading and spelling impairment.

Dissociation of long-term verbal memory and fronto-executive impairment in first-episode psychosis

PubMed Central

Leeson, V. C.; Robbins, T. W.; Franklin, C.; Harrison, M.; Harrison, I.; Ron, M. A.; Barnes, T. R. E.; Joyce, E. M.

2009-01-01

Background Verbal memory is frequently and severely affected in schizophrenia and has been implicated as a mediator of poor clinical outcome. Whereas encoding deficits are well demonstrated, it is unclear whether retention is impaired. This distinction is important because accelerated forgetting implies impaired consolidation attributable to medial temporal lobe (MTL) dysfunction whereas impaired encoding and retrieval implicates involvement of prefrontal cortex. Method We assessed a group of healthy volunteers (n=97) and pre-morbid IQ- and sex-matched first-episode psychosis patients (n=97), the majority of whom developed schizophrenia. We compared performance of verbal learning and recall with measures of visuospatial working memory, planning and attentional set-shifting, and also current IQ. Results All measures of performance, including verbal memory retention, a memory savings score that accounted for learning impairments, were significantly impaired in the schizophrenia group. The difference between groups for delayed recall remained even after the influence of learning and recall was accounted for. Factor analyses showed that, in patients, all variables except verbal memory retention loaded on a single factor, whereas in controls verbal memory and fronto-executive measures were separable. Conclusions The results suggest that IQ, executive function and verbal learning deficits in schizophrenia may reflect a common abnormality of information processing in prefrontal cortex rather than specific impairments in different cognitive domains. Verbal memory retention impairments, however, may have a different aetiology. PMID:19419594

Aberrant temporal behavior of mismatch negativity generators in schizophrenia patients and subjects at clinical high risk for psychosis.

PubMed

Kim, Minah; Cho, Kang Ik Kevin; Yoon, Youngwoo Bryan; Lee, Tae Young; Kwon, Jun Soo

2017-02-01

Although disconnection syndrome has been considered a core pathophysiologic mechanism of schizophrenia, little is known about the temporal behavior of mismatch negativity (MMN) generators in individuals with schizophrenia or clinical high risk (CHR) for psychosis. MMN was assessed in 29 schizophrenia patients, 40 CHR subjects, and 47 healthy controls (HCs). Individual realistic head models and the minimum L2 norm algorithm were used to generate a current source density (CSD) model of MMN. The strength and time course of MMN CSD activity were calculated separately for the frontal and temporal cortices and were compared across brain regions and groups. Schizophrenia patients and CHR subjects displayed lower MMN CSD strength than HCs in both the temporal and frontal cortices. We found a significant time delay in MMN generator activity in the frontal cortex relative to that in the temporal cortex in HCs. However, the sequential temporo-frontal activities of MMN generators were disrupted in both the schizophrenia and CHR groups. Impairments and altered temporal behavior of MMN multiple generators were observed even in individuals at risk for psychosis. These findings suggest that aberrant MMN generator activity might be helpful in revealing the pathophysiology of schizophrenia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Aβ25-35 injection into the temporal cortex induces chronic inflammation that contributes to neurodegeneration and spatial memory impairment in rats.

PubMed

Diaz, Alfonso; Limon, Daniel; Chávez, Raúl; Zenteno, Edgar; Guevara, Jorge

2012-01-01

Amyloid-β (Aβ)25-35 is able to cause memory impairment and neurodegenerative events. Recent evidence has shown that the injection of Aβ25-35 into the temporal cortex (TCx) of rats increases the inflammatory response; however, it is unclear how the inflammatory process could be involved in the progression of Aβ25-35 toxicity. In this study we investigated the role of inflammation in the neuronal damage and spatial memory impairment generated by Aβ25-35 in rat TCx using immunohistochemistry, ELISA, and a behavioral test in the radial maze. Our findings show that Aβ25-35 -injection into the TCx induced a reactive gliosis (GFAP and CD11b-reactivity) and an increase of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) in the TCx and the hippocampus at 5, 15, and 30 days after injection. Thirty days after Aβ25-35 injection, we observed that the inflammatory reaction probably contributed to increase the immunoreactivity of inducible nitric oxide synthase and nitrite levels, as well as to the loss of neurons in TCx and hippocampus. Behavioral performance showed that the neurodegeneration evoked by Aβ25-35 delayed acquisition of learning and impaired spatial memory, because the Aβ25-35-treated animals showed a greater number of errors during the task than the control group. Previous administration of an interleukin receptor antagonist (IL-1ra) (10 and 20 μg/μL, into TCx), an anti-inflammatory agent, suppressed the Aβ25-35-induced inflammatory response and neurodegeneration, as well as memory dysfunction. This study suggests that the chronic inflammatory reaction could contribute to the progression of Aβ25-35 toxicity and cause cognitive impairment.

Dyslexic children show short-term memory deficits in phonological storage and serial rehearsal: an fMRI study.

PubMed

Beneventi, Harald; Tønnessen, Finn Egil; Ersland, Lars

2009-01-01

Dyslexia is primarily associated with a phonological processing deficit. However, the clinical manifestation also includes a reduced verbal working memory (WM) span. It is unclear whether this WM impairment is caused by the phonological deficit or a distinct WM deficit. The main aim of this study was to investigate neuronal activation related to phonological storage and rehearsal of serial order in WM in a sample of 13-year-old dyslexic children compared with age-matched nondyslexic children. A sequential verbal WM task with two tasks was used. In the Letter Probe task, the probe consisted of a single letter and the judgment was for the presence or absence of that letter in the prior sequence of six letters. In the Sequence Probe (SP) task, the probe consisted of all six letters and the judgment was for a match of their serial order with the temporal order in the prior sequence. Group analyses as well as single-subject analysis were performed with the statistical parametric mapping software SPM2. In the Letter Probe task, the dyslexic readers showed reduced activation in the left precentral gyrus (BA6) compared to control group. In the Sequence Probe task, the dyslexic readers showed reduced activation in the prefrontal cortex and the superior parietal cortex (BA7) compared to the control subjects. Our findings suggest that a verbal WM impairment in dyslexia involves an extended neural network including the prefrontal cortex and the superior parietal cortex. Reduced activation in the left BA6 in both the Letter Probe and Sequence Probe tasks may be caused by a deficit in phonological processing. However, reduced bilateral activation in the BA7 in the Sequence Probe task only could indicate a distinct working memory deficit in dyslexia associated with temporal order processing.

Preserved semantic access in global amnesia and hippocampal damage.

PubMed

Giovagnoli, A R; Erbetta, A; Bugiani, O

2001-12-01

C.B., a right-handed 33-year-old man, presented with anterograde amnesia after acute heart block. Cognitive abilities were normal except for serious impairment of long-term episodic memory. The access to semantic information was fully preserved. Magnetic resonance showed high signal intensity and marked volume loss in the hippocampus bilaterally; the left and right parahippocampal gyrus, lateral occipito-temporal gyrus, inferior temporal gyrus, and lateral temporal cortex were normal. This case underlines that global amnesia associated with hippocampal damage does not affect semantic memory. Although the hippocampus is important in retrieving context-linked information, its role is not so crucial in retrieving semantic contents. Cortical areas surrounding the hippocampus and lateral temporal areas might guide the recall of semantic information.

Refinement of learned skilled movement representation in motor cortex deep output layer

PubMed Central

Li, Qian; Ko, Ho; Qian, Zhong-Ming; Yan, Leo Y. C.; Chan, Danny C. W.; Arbuthnott, Gordon; Ke, Ya; Yung, Wing-Ho

2017-01-01

The mechanisms underlying the emergence of learned motor skill representation in primary motor cortex (M1) are not well understood. Specifically, how motor representation in the deep output layer 5b (L5b) is shaped by motor learning remains virtually unknown. In rats undergoing motor skill training, we detect a subpopulation of task-recruited L5b neurons that not only become more movement-encoding, but their activities are also more structured and temporally aligned to motor execution with a timescale of refinement in tens-of-milliseconds. Field potentials evoked at L5b in vivo exhibit persistent long-term potentiation (LTP) that parallels motor performance. Intracortical dopamine denervation impairs motor learning, and disrupts the LTP profile as well as the emergent neurodynamical properties of task-recruited L5b neurons. Thus, dopamine-dependent recruitment of L5b neuronal ensembles via synaptic reorganization may allow the motor cortex to generate more temporally structured, movement-encoding output signal from M1 to downstream circuitry that drives increased uniformity and precision of movement during motor learning. PMID:28598433

Necroptosis Resumes Apoptosis in Hippocampus but Not in Frontal Cortex.

PubMed

Nikseresht, Sara; Khodagholi, Fariba; Dargahi, Leila; Ahmadiani, Abolhassan

2017-12-01

Cell death subsequent to or concurrent with neuroinflammation results in some damages like neuron loss and spatial memory impairment. In this study, we demonstrated the temporal pattern of neuroinflammation, necroptotic, and apoptotic cell deaths in hippocampus and frontal cortex following intracerebroventricular administration of lipopolysaccharide (LPS). We evaluated receptor interacting protein kinase 1 (RIP1), RIP3, and two related metabolic enzymes including glutamate-ammonia ligase (GLUL) and glutamate dehydrogenase (GLUD) as necroptosis factors. Apoptosis pathway, antioxidant status and inflammatory cytokines were also assessed. Based on the probable role of these brain regions in working memory performance, spontaneous alternation was evaluated through the Y-maze apparatus. RIP1, RIP3, and then GLUL and GLUD, as well as apoptosis markers, inflammatory regulators, and antioxidant defense demonstrated different time-dependent patterns in hippocampus and frontal cortex. Interestingly, in hippocampus but not in frontal cortex, necroptosis resumed apoptosis. Our results in behavioral section revealed that neuroinflammation along with apoptosis and necroptosis pathways could lead to reversible short-term memory impairment after LPS injection. In conclusion, it can be suggested that there is a region-specific response of cell deaths regulators activation in hippocampus and frontal cortex. In addition, elucidating the time profile of events in response to neuroinflammation would be of great help in mechanistic studies and understanding of pathways interaction. J. Cell. Biochem. 118: 4628-4638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Lexical-semantic processing in the semantic priming paradigm in aphasic patients.

PubMed

Salles, Jerusa Fumagalli de; Holderbaum, Candice Steffen; Parente, Maria Alice Mattos Pimenta; Mansur, Letícia Lessa; Ansaldo, Ana Inès

2012-09-01

There is evidence that the explicit lexical-semantic processing deficits which characterize aphasia may be observed in the absence of implicit semantic impairment. The aim of this article was to critically review the international literature on lexical-semantic processing in aphasia, as tested through the semantic priming paradigm. Specifically, this review focused on aphasia and lexical-semantic processing, the methodological strengths and weaknesses of the semantic paradigms used, and recent evidence from neuroimaging studies on lexical-semantic processing. Furthermore, evidence on dissociations between implicit and explicit lexical-semantic processing reported in the literature will be discussed and interpreted by referring to functional neuroimaging evidence from healthy populations. There is evidence that semantic priming effects can be found both in fluent and in non-fluent aphasias, and that these effects are related to an extensive network which includes the temporal lobe, the pre-frontal cortex, the left frontal gyrus, the left temporal gyrus and the cingulated cortex.

Functional integrity of the retrosplenial cortex is essential for rapid consolidation and recall of fear memory.

PubMed

Katche, Cynthia; Dorman, Guido; Slipczuk, Leandro; Cammarota, Martín; Medina, Jorge H

2013-03-15

Memory storage is a temporally graded process involving different phases and different structures in the mammalian brain. Cortical plasticity is essential to store stable memories, but little is known regarding its involvement in memory processing. Here we show that fear memory consolidation requires early post-training macromolecular synthesis in the anterior part of the retrosplenial cortex (aRSC), and that reversible pharmacological inactivation of this cortical region impairs recall of recent as well as of remote memories. These results challenge the generally accepted idea that neocortical areas are slow encoding systems that participate in the retrieval of remote memories only.

Voxel-based comparison of brain glucose metabolism between patients with Cushing's disease and healthy subjects.

PubMed

Liu, Shuai; Wang, Yinyan; Xu, Kaibin; Ping, Fan; Li, Fang; Wang, Renzhi; Cheng, Xin

2018-01-01

Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD) owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG PET), between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up.

Postictal psychosis and its electrophysiological correlates in invasive EEG: a case report study and literature review.

PubMed

Kuba, Robert; Brázdil, Milan; Rektor, Ivan

2012-04-01

We identified two patients with medically refractory temporal lobe epilepsy, from whom intracranial EEG recordings were obtained at the time of postictal psychosis. Both patients had mesial temporal epilepsy associated with hippocampal sclerosis. In both patients, the postictal psychosis was associated with a continual "epileptiform" EEG pattern that differed from their interictal and ictal EEG findings (rhythmical slow wave and "abortive" spike-slow wave complex activity in the right hippocampus and lateral temporal cortex in case 1 and a periodic pattern of triphasic waves in the contacts recording activity from the left anterior cingulate gyrus). Some cases of postictal psychosis might be caused by the transient impairment of several limbic system structures due to the "continual epileptiform discharge" in some brain regions. Case 2 is the first report of a patient with TLE in whom psychotic symptoms were associated with the epileptiform impairment of the anterior cingulate gyrus. Copyright © 2012 Elsevier Inc. All rights reserved.

Effective Connectivity from Early Visual Cortex to Posterior Occipitotemporal Face Areas Supports Face Selectivity and Predicts Developmental Prosopagnosia

PubMed Central

Garrido, Lucia; Driver, Jon; Dolan, Raymond J.; Duchaine, Bradley C.; Furl, Nicholas

2016-01-01

Face processing is mediated by interactions between functional areas in the occipital and temporal lobe, and the fusiform face area (FFA) and anterior temporal lobe play key roles in the recognition of facial identity. Individuals with developmental prosopagnosia (DP), a lifelong face recognition impairment, have been shown to have structural and functional neuronal alterations in these areas. The present study investigated how face selectivity is generated in participants with normal face processing, and how functional abnormalities associated with DP, arise as a function of network connectivity. Using functional magnetic resonance imaging and dynamic causal modeling, we examined effective connectivity in normal participants by assessing network models that include early visual cortex (EVC) and face-selective areas and then investigated the integrity of this connectivity in participants with DP. Results showed that a feedforward architecture from EVC to the occipital face area, EVC to FFA, and EVC to posterior superior temporal sulcus (pSTS) best explained how face selectivity arises in both controls and participants with DP. In this architecture, the DP group showed reduced connection strengths on feedforward connections carrying face information from EVC to FFA and EVC to pSTS. These altered network dynamics in DP contribute to the diminished face selectivity in the posterior occipitotemporal areas affected in DP. These findings suggest a novel view on the relevance of feedforward projection from EVC to posterior occipitotemporal face areas in generating cortical face selectivity and differences in face recognition ability. SIGNIFICANCE STATEMENT Areas of the human brain showing enhanced activation to faces compared to other objects or places have been extensively studied. However, the factors leading to this face selectively have remained mostly unknown. We show that effective connectivity from early visual cortex to posterior occipitotemporal face areas gives rise to face selectivity. Furthermore, people with developmental prosopagnosia, a lifelong face recognition impairment, have reduced face selectivity in the posterior occipitotemporal face areas and left anterior temporal lobe. We show that this reduced face selectivity can be predicted by effective connectivity from early visual cortex to posterior occipitotemporal face areas. This study presents the first network-based account of how face selectivity arises in the human brain. PMID:27030766

Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging.

PubMed

Maass, Anne; Lockhart, Samuel N; Harrison, Theresa M; Bell, Rachel K; Mellinger, Taylor; Swinnerton, Kaitlin; Baker, Suzanne L; Rabinovici, Gil D; Jagust, William J

2018-01-17

The medial temporal lobe (MTL) is an early site of tau accumulation and MTL dysfunction may underlie episodic-memory decline in aging and dementia. Postmortem data indicate that tau pathology in the transentorhinal cortex is common by age 60, whereas spread to neocortical regions and worsening of cognition is associated with β-amyloid (Aβ). We used [ 18 F]AV-1451 and [ 11 C]PiB positron emission tomography, structural MRI, and neuropsychological assessment to investigate how in vivo tau accumulation in temporal lobe regions, Aβ, and MTL atrophy contribute to episodic memory in cognitively normal older adults ( n = 83; age, 77 ± 6 years; 58% female). Stepwise regressions identified tau in MTL regions known to be affected in old age as the best predictor of episodic-memory performance independent of Aβ status. There was no interactive effect of MTL tau with Aβ on memory. Higher MTL tau was related to higher age in the subjects without evidence of Aβ. Among temporal lobe subregions, episodic memory was most strongly related to tau-tracer uptake in the parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our parcellation includes the transentorhinal cortex. In subjects with longitudinal MRI and cognitive data ( n = 57), entorhinal atrophy mirrored patterns of tau pathology and their relationship with memory decline. Our data are consistent with neuropathological studies and further suggest that entorhinal tau pathology underlies memory decline in old age even without Aβ. SIGNIFICANCE STATEMENT Tau tangles and β-amyloid (Aβ) plaques are key lesions in Alzheimer's disease (AD) but both pathologies also occur in cognitively normal older people. Neuropathological data indicate that tau tangles in the medial temporal lobe (MTL) underlie episodic-memory impairments in AD dementia. However, it remains unclear whether MTL tau pathology also accounts for memory impairments often seen in elderly people and how Aβ affects this relationship. Using tau-specific and Aβ-specific positron emission tomography tracers, we show that in vivo MTL tau pathology is associated with episodic-memory performance and MTL atrophy in cognitively normal adults, independent of Aβ. Our data point to MTL tau pathology, particularly in the entorhinal cortex, as a substrate of age-related episodic-memory loss. Copyright © 2018 the authors 0270-6474/18/380530-14$15.00/0.

Gray matter alteration in isolated congenital anosmia patient: a voxel-based morphometry study.

PubMed

Yao, Linyin; Yi, Xiaoli; Wei, Yongxiang

2013-09-01

Decreased volume of gray matter (GM) was observed in olfactory loss in patients with neurodegenerative disorder. However, GM volume has not yet been investigated in isolated congenital anosmia (ICA) people. We herewith investigated the volume change of gray matter of an ICA boy by morphometric analysis of magnetic resonance images (voxel-based morphometry), and compared with that of 20 age-matched healthy controls. ICA boy presented a significant decrease in GM volume in the orbitofrontal cortex, anterior cingulate cortex, middle cingulate cortex, thalamus, insular cortex, cerebellum, precuneus, gyrus rectus, subcallosal gyrus, middle temporal gyrus, fusiform gyrus and piriform cortex. No significant GM volume increase was detected in other brain areas. The pattern of GM atrophy was similar as previous literature reported. Our results identified similar GM volume alterations regardless of the causes of olfactory impairment. Decreased GM volume was not only shown in olfactory bulbs, olfactory tracts and olfactory sulcus, also in primary olfactory cortex and the secondary cerebral olfactory areas in ICA people. This is the first study to evaluate GM volume alterations in ICA people.

Type 1 Diabetes and Impaired Awareness of Hypoglycemia Are Associated with Reduced Brain Gray Matter Volumes.

PubMed

Bednarik, Petr; Moheet, Amir A; Grohn, Heidi; Kumar, Anjali F; Eberly, Lynn E; Seaquist, Elizabeth R; Mangia, Silvia

2017-01-01

In this study, we retrospectively analyzed the anatomical MRI data acquired from 52 subjects with type 1 diabetes (26M/26F, 36 ± 11 years old, A1C = 7.2 ± 0.9%) and 50 age, sex and BMI frequency-matched non-diabetic controls (25M/25F, 36 ± 14 years old). The T1D group was further sub-divided based on whether subjects had normal, impaired, or indeterminate awareness of hypoglycemia ( n = 31, 20, and 1, respectively). Our goals were to test whether the gray matter (GM) volumes of selected brain regions were associated with diabetes status as well as with the status of hypoglycemia awareness. T1D subjects were found to have slightly smaller volume of the whole cortex as compared to controls (-2.7%, p = 0.016), with the most affected brain region being the frontal lobe (-3.6%, p = 0.024). Similar differences of even larger magnitude were observed among the T1D subjects based on their hypoglycemia awareness status. Indeed, compared to the patients with normal awareness of hypoglycemia, patients with impaired awareness had smaller volume of the whole cortex (-7.9%, p = 0.0009), and in particular of the frontal lobe (-9.1%, p = 0.006), parietal lobe (-8.0%, p = 0.015) and temporal lobe (-8.2%, p = 0.009). Such differences were very similar to those observed between patients with impaired awareness and controls (-7.6%, p = 0.0002 in whole cortex, -9.1%, p = 0.0003 in frontal lobe, -7.8%, p = 0.002 in parietal lobe, and -6.4%, p = 0.019 in temporal lobe). On the other hand, patients with normal awareness did not present significant volume differences compared to controls. No group-differences were observed in the occipital lobe or in the anterior cingulate, posterior cingulate, hippocampus, and thalamus. We conclude that diabetes status is associated with a small but statistically significant reduction of the whole cortex volume, mainly in the frontal lobe. The most prominent structural effects occurred in patients with impaired awareness of hypoglycemia (IAH) as compared to those with normal awareness, perhaps due to the long-term exposure to recurrent episodes of hypoglycemia. Future studies aimed at quantifying relationships of structural outcomes with functional outcomes, with cognitive performance, as well as with parameters describing glucose variability and severity of hypoglycemia episodes, will be necessary to further understand the impact of T1D on the brain.

Neural correlates of cognitive dysfunction in Lewy body diseases and tauopathies: combined assessment with FDG-PET and the CERAD test battery.

PubMed

Hellwig, Sabine; Frings, Lars; Bormann, Tobias; Kreft, Annabelle; Amtage, Florian; Spehl, Timo S; Weiller, Cornelius; Tüscher, Oliver; Meyer, Philipp T

2013-11-01

We investigated disease-specific cognitive profiles and their neural correlates in Lewy-body diseases (LBD) and tauopathies by CERAD assessment and FDG-PET. Analyses revealed a significant interaction between reduced semantic fluency in tauopathies and impaired verbal learning in LBD. Semantic fluency discriminated between groups with high accuracy (83%). Compared to LBD, tauopathy patients showed bilateral hypometabolism of midbrain, thalamus, middle cingulate gyrus and supplementary motor/premotor cortex. In the reverse contrast, LBD patients exhibited bilateral hypometabolism in posterior parietal cortex, precuneus and inferior temporal gyrus extending into occipital and frontal cortices. In diagnosis-independent voxel-based analyses, verbal learning/memory correlated with left temporal and right parietal metabolism, while fluency was coupled to bilateral striatal and frontal metabolism. Naming correlated with left frontal metabolism and drawing with metabolism in bilateral temporal and left frontal regions. In line with disease-specific patterns of regional glucose metabolism, tauopathies and LBD show distinct cognitive profiles, which may assist clinical differentiation. Copyright © 2013 Elsevier Inc. All rights reserved.

Trait impulsivity and impaired prefrontal impulse inhibition function in adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study.

PubMed

Ding, Wei-na; Sun, Jin-hua; Sun, Ya-Wen; Chen, Xue; Zhou, Yan; Zhuang, Zhi-guo; Li, Lei; Zhang, Yong; Xu, Jian-rong; Du, Ya-song

2014-05-30

Recent studies suggest that Internet gaming addiction (IGA) is an impulse disorder, or is at least related to impulse control disorders. In the present study, we hypothesized that different facets of trait impulsivity may be specifically linked to the brain regions with impaired impulse inhibition function in IGA adolescents. Seventeen adolescents with IGA and seventeen healthy controls were scanned during performance of a response-inhibition Go/No-Go task using a 3.0 T MRI scanner. The Barratt Impulsiveness Scale (BIS)-11 was used to assess impulsivity. There were no differences in the behavioral performance on the Go/No-Go task between the groups. However, the IGA group was significantly hyperactive during No-Go trials in the left superior medial frontal gyrus, right anterior cingulate cortex, right superior/middle frontal gyrus, left inferior parietal lobule, left precentral gyrus, and left precuneus and cuneus. Further, the bilateral middle temporal gyrus, bilateral inferior temporal gyrus, and right superior parietal lobule were significantly hypoactive during No-Go trials. Activation of the left superior medial frontal gyrus was positively associated with BIS-11 and Chen Internet Addiction Scale (CIAS) total score across IGA participants. Our data suggest that the prefrontal cortex may be involved in the circuit modulating impulsivity, while its impaired function may relate to high impulsivity in adolescents with IGA, which may contribute directly to the Internet addiction process.

Trait impulsivity and impaired prefrontal impulse inhibition function in adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study

PubMed Central

2014-01-01

Background Recent studies suggest that Internet gaming addiction (IGA) is an impulse disorder, or is at least related to impulse control disorders. In the present study, we hypothesized that different facets of trait impulsivity may be specifically linked to the brain regions with impaired impulse inhibition function in IGA adolescents. Methods Seventeen adolescents with IGA and seventeen healthy controls were scanned during performance of a response-inhibition Go/No-Go task using a 3.0 T MRI scanner. The Barratt Impulsiveness Scale (BIS)-11 was used to assess impulsivity. Results There were no differences in the behavioral performance on the Go/No-Go task between the groups. However, the IGA group was significantly hyperactive during No-Go trials in the left superior medial frontal gyrus, right anterior cingulate cortex, right superior/middle frontal gyrus, left inferior parietal lobule, left precentral gyrus, and left precuneus and cuneus. Further, the bilateral middle temporal gyrus, bilateral inferior temporal gyrus, and right superior parietal lobule were significantly hypoactive during No-Go trials. Activation of the left superior medial frontal gyrus was positively associated with BIS-11 and Chen Internet Addiction Scale (CIAS) total score across IGA participants. Conclusions Our data suggest that the prefrontal cortex may be involved in the circuit modulating impulsivity, while its impaired function may relate to high impulsivity in adolescents with IGA, which may contribute directly to the Internet addiction process. PMID:24885073

The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes.

PubMed

Dunn, Joel T; Choudhary, Pratik; Teh, Ming Ming; Macdonald, Ian; Hunt, Katharine F; Marsden, Paul K; Amiel, Stephanie A

2018-05-12

Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes increases the risk of severe hypoglycaemia sixfold and can be resistant to intervention. We explored the impact of IAH on central responses to hypoglycaemia to investigate the mechanisms underlying barriers to therapeutic intervention. We conducted [ 15 O]water positron emission tomography studies of regional brain perfusion during euglycaemia (target 5 mmol/l), hypoglycaemia (achieved level, 2.4 mmol/l) and recovery (target 5 mmol/l) in 17 men with type 1 diabetes: eight with IAH, and nine with intact hypoglycaemia awareness (HA). Hypoglycaemia with HA was associated with increased activation in brain regions including the thalamus, insula, globus pallidus (GP), anterior cingulate cortex (ACC), orbital cortex, dorsolateral frontal (DLF) cortex, angular gyrus and amygdala; deactivation occurred in the temporal and parahippocampal regions. IAH was associated with reduced catecholamine and symptom responses to hypoglycaemia vs HA (incremental AUC: autonomic scores, 26.2 ± 35.5 vs 422.7 ± 237.1; neuroglycopenic scores, 34.8 ± 88.8 vs 478.9 ± 311.1; both p < 0.002). There were subtle differences (p < 0.005, k ≥ 50 voxels) in brain activation at hypoglycaemia, including early differences in the right central operculum, bilateral medial orbital (MO) cortex, and left posterior DLF cortex, with additional differences in the ACC, right GP and post- and pre-central gyri in established hypoglycaemia, and lack of deactivation in temporal regions in established hypoglycaemia. Differences in activation in the post- and pre-central gyri may be expected in people with reduced subjective responses to hypoglycaemia. Alterations in the activity of regions involved in the drive to eat (operculum), emotional salience (MO cortex), aversion (GP) and recall (temporal) suggest differences in the perceived importance and urgency of responses to hypoglycaemia in IAH compared with HA, which may be key to the persistence of the condition.

Pure word deafness with auditory object agnosia after bilateral lesion of the superior temporal sulcus.

PubMed

Gutschalk, Alexander; Uppenkamp, Stefan; Riedel, Bernhard; Bartsch, Andreas; Brandt, Tobias; Vogt-Schaden, Marlies

2015-12-01

Based on results from functional imaging, cortex along the superior temporal sulcus (STS) has been suggested to subserve phoneme and pre-lexical speech perception. For vowel classification, both superior temporal plane (STP) and STS areas have been suggested relevant. Lesion of bilateral STS may conversely be expected to cause pure word deafness and possibly also impaired vowel classification. Here we studied a patient with bilateral STS lesions caused by ischemic strokes and relatively intact medial STPs to characterize the behavioral consequences of STS loss. The patient showed severe deficits in auditory speech perception, whereas his speech production was fluent and communication by written speech was grossly intact. Auditory-evoked fields in the STP were within normal limits on both sides, suggesting that major parts of the auditory cortex were functionally intact. Further studies showed that the patient had normal hearing thresholds and only mild disability in tests for telencephalic hearing disorder. Prominent deficits were discovered in an auditory-object classification task, where the patient performed four standard deviations below the control group. In marked contrast, performance in a vowel-classification task was intact. Auditory evoked fields showed enhanced responses for vowels compared to matched non-vowels within normal limits. Our results are consistent with the notion that cortex along STS is important for auditory speech perception, although it does not appear to be entirely speech specific. Formant analysis and single vowel classification, however, appear to be already implemented in auditory cortex on the STP. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional Mapping of the Human Auditory Cortex: fMRI Investigation of a Patient with Auditory Agnosia from Trauma to the Inferior Colliculus.

PubMed

Poliva, Oren; Bestelmeyer, Patricia E G; Hall, Michelle; Bultitude, Janet H; Koller, Kristin; Rafal, Robert D

2015-09-01

To use functional magnetic resonance imaging to map the auditory cortical fields that are activated, or nonreactive, to sounds in patient M.L., who has auditory agnosia caused by trauma to the inferior colliculi. The patient cannot recognize speech or environmental sounds. Her discrimination is greatly facilitated by context and visibility of the speaker's facial movements, and under forced-choice testing. Her auditory temporal resolution is severely compromised. Her discrimination is more impaired for words differing in voice onset time than place of articulation. Words presented to her right ear are extinguished with dichotic presentation; auditory stimuli in the right hemifield are mislocalized to the left. We used functional magnetic resonance imaging to examine cortical activations to different categories of meaningful sounds embedded in a block design. Sounds activated the caudal sub-area of M.L.'s primary auditory cortex (hA1) bilaterally and her right posterior superior temporal gyrus (auditory dorsal stream), but not the rostral sub-area (hR) of her primary auditory cortex or the anterior superior temporal gyrus in either hemisphere (auditory ventral stream). Auditory agnosia reflects dysfunction of the auditory ventral stream. The ventral and dorsal auditory streams are already segregated as early as the primary auditory cortex, with the ventral stream projecting from hR and the dorsal stream from hA1. M.L.'s leftward localization bias, preserved audiovisual integration, and phoneme perception are explained by preserved processing in her right auditory dorsal stream.

Underconnectivity between voice-selective cortex and reward circuitry in children with autism.

PubMed

Abrams, Daniel A; Lynch, Charles J; Cheng, Katherine M; Phillips, Jennifer; Supekar, Kaustubh; Ryali, Srikanth; Uddin, Lucina Q; Menon, Vinod

2013-07-16

Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.

Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

PubMed

Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

2008-02-01

To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I =

Working memory network plasticity after anterior temporal lobe resection: a longitudinal functional magnetic resonance imaging study

PubMed Central

Stretton, Jason; Sidhu, Meneka K.; Winston, Gavin P.; Bartlett, Philippa; McEvoy, Andrew W.; Symms, Mark R.; Koepp, Matthias J.; Thompson, Pamela J.

2014-01-01

Working memory is a crucial cognitive function that is disrupted in temporal lobe epilepsy. It is unclear whether this impairment is a consequence of temporal lobe involvement in working memory processes or due to seizure spread to extratemporal eloquent cortex. Anterior temporal lobe resection controls seizures in 50–80% of patients with drug-resistant temporal lobe epilepsy and the effect of surgery on working memory are poorly understood both at a behavioural and neural level. We investigated the impact of temporal lobe resection on the efficiency and functional anatomy of working memory networks. We studied 33 patients with unilateral medial temporal lobe epilepsy (16 left) before, 3 and 12 months after anterior temporal lobe resection. Fifteen healthy control subjects were also assessed in parallel. All subjects had neuropsychological testing and performed a visuospatial working memory functional magnetic resonance imaging paradigm on these three separate occasions. Changes in activation and deactivation patterns were modelled individually and compared between groups. Changes in task performance were included as regressors of interest to assess the efficiency of changes in the networks. Left and right temporal lobe epilepsy patients were impaired on preoperative measures of working memory compared to controls. Working memory performance did not decline following left or right temporal lobe resection, but improved at 3 and 12 months following left and, to a lesser extent, following right anterior temporal lobe resection. After left anterior temporal lobe resection, improved performance correlated with greater deactivation of the left hippocampal remnant and the contralateral right hippocampus. There was a failure of increased deactivation of the left hippocampal remnant at 3 months after left temporal lobe resection compared to control subjects, which had normalized 12 months after surgery. Following right anterior temporal lobe resection there was a progressive increase of activation in the right superior parietal lobe at 3 and 12 months after surgery. There was greater deactivation of the right hippocampal remnant compared to controls between 3 and 12 months after right anterior temporal lobe resection that was associated with lesser improvement in task performance. Working memory improved after anterior temporal lobe resection, particularly following left-sided resections. Postoperative working memory was reliant on the functional capacity of the hippocampal remnant and, following left resections, the functional reserve of the right hippocampus. These data suggest that working memory following temporal lobe resection is dependent on the engagement of the posterior medial temporal lobes and eloquent cortex. PMID:24691395

Strategies for tonal and atonal musical interpretation in blind and normally sighted children: an fMRI study.

PubMed

Guerrero Arenas, Coral; Hidalgo Tobón, Silvia S; Dies Suarez, Pilar; Barragán Pérez, Eduardo; Castro Sierra, Eduardo; García, Julio; de Celis Alonso, Benito

2016-04-01

Early childhood is known to be a period when cortical plasticity phenomena are at a maximum. Music is a stimulus known to modulate these mechanisms. On the other hand, neurological impairments like blindness are also known to affect cortical plasticity. Here, we address how tonal and atonal musical stimuli are processed in control and blind young children. We aimed to understand the differences between the two groups when processing this physiological information. Atonal stimuli produced larger activations in cerebellum, fusiform, and temporal lobe structures than tonal. In contrast, tonal stimuli induced larger frontal lobe representations than atonal. Control participants presented large activations in cerebellum, fusiform, and temporal lobe. A correlation/connectivity study showed that the blind group incorporated larger amounts of perceptual information (somatosensory and motor) into tonal processing through the function of the anterior prefrontal cortex (APC). They also used the visual cortex in conjunction with the Wernicke's area to process this information. In contrast, controls processed sound with perceptual stimuli from auditory cortex structures (including Wernicke's area). In this case, information was processed through the dorsal posterior cingulate cortex and not the APC. The orbitofrontal cortex also played a key role for atonal interpretation in this group. Wernicke's area, known to be involved in speech, was heavily involved for both groups and all stimuli. The two groups presented clear differences in strategies for music processing, with very different recruitment of brain regions.

Preserved feedforward but impaired top-down processes in the vegetative state.

PubMed

Boly, Melanie; Garrido, Marta Isabel; Gosseries, Olivia; Bruno, Marie-Aurélie; Boveroux, Pierre; Schnakers, Caroline; Massimini, Marcello; Litvak, Vladimir; Laureys, Steven; Friston, Karl

2011-05-13

Frontoparietal cortex is involved in the explicit processing (awareness) of stimuli. Frontoparietal activation has also been found in studies of subliminal stimulus processing. We hypothesized that an impairment of top-down processes, involved in recurrent neuronal message-passing and the generation of long-latency electrophysiological responses, might provide a more reliable correlate of consciousness in severely brain-damaged patients, than frontoparietal responses. We measured effective connectivity during a mismatch negativity paradigm and found that the only significant difference between patients in a vegetative state and controls was an impairment of backward connectivity from frontal to temporal cortices. This result emphasizes the importance of top-down projections in recurrent processing that involve high-order associative cortices for conscious perception.

Neuronal correlates of theory of mind and empathy: a functional magnetic resonance imaging study in a nonverbal task.

PubMed

Völlm, Birgit A; Taylor, Alexander N W; Richardson, Paul; Corcoran, Rhiannon; Stirling, John; McKie, Shane; Deakin, John F W; Elliott, Rebecca

2006-01-01

Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal pole in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from Sarfati et al. (1997) [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. Schizophrenia Research 25, 199-209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal poles. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy.

Fundamental deficits of auditory perception in Wernicke's aphasia.

PubMed

Robson, Holly; Grube, Manon; Lambon Ralph, Matthew A; Griffiths, Timothy D; Sage, Karen

2013-01-01

This work investigates the nature of the comprehension impairment in Wernicke's aphasia (WA), by examining the relationship between deficits in auditory processing of fundamental, non-verbal acoustic stimuli and auditory comprehension. WA, a condition resulting in severely disrupted auditory comprehension, primarily occurs following a cerebrovascular accident (CVA) to the left temporo-parietal cortex. Whilst damage to posterior superior temporal areas is associated with auditory linguistic comprehension impairments, functional-imaging indicates that these areas may not be specific to speech processing but part of a network for generic auditory analysis. We examined analysis of basic acoustic stimuli in WA participants (n = 10) using auditory stimuli reflective of theories of cortical auditory processing and of speech cues. Auditory spectral, temporal and spectro-temporal analysis was assessed using pure-tone frequency discrimination, frequency modulation (FM) detection and the detection of dynamic modulation (DM) in "moving ripple" stimuli. All tasks used criterion-free, adaptive measures of threshold to ensure reliable results at the individual level. Participants with WA showed normal frequency discrimination but significant impairments in FM and DM detection, relative to age- and hearing-matched controls at the group level (n = 10). At the individual level, there was considerable variation in performance, and thresholds for both FM and DM detection correlated significantly with auditory comprehension abilities in the WA participants. These results demonstrate the co-occurrence of a deficit in fundamental auditory processing of temporal and spectro-temporal non-verbal stimuli in WA, which may have a causal contribution to the auditory language comprehension impairment. Results are discussed in the context of traditional neuropsychology and current models of cortical auditory processing. Copyright © 2012 Elsevier Ltd. All rights reserved.

The posterior parietal cortex in recognition memory: a neuropsychological study.

PubMed

Haramati, Sharon; Soroker, Nachum; Dudai, Yadin; Levy, Daniel A

2008-01-01

Several recent functional neuroimaging studies have reported robust bilateral activation (L>R) in lateral posterior parietal cortex and precuneus during recognition memory retrieval tasks. It has not yet been determined what cognitive processes are represented by those activations. In order to examine whether parietal lobe-based processes are necessary for basic episodic recognition abilities, we tested a group of 17 first-incident CVA patients whose cortical damage included (but was not limited to) extensive unilateral posterior parietal lesions. These patients performed a series of tasks that yielded parietal activations in previous fMRI studies: yes/no recognition judgments on visual words and on colored object pictures and identifiable environmental sounds. We found that patients with left hemisphere lesions were not impaired compared to controls in any of the tasks. Patients with right hemisphere lesions were not significantly impaired in memory for visual words, but were impaired in recognition of object pictures and sounds. Two lesion--behavior analyses--area-based correlations and voxel-based lesion symptom mapping (VLSM)---indicate that these impairments resulted from extra-parietal damage, specifically to frontal and lateral temporal areas. These findings suggest that extensive parietal damage does not impair recognition performance. We suggest that parietal activations recorded during recognition memory tasks might reflect peri-retrieval processes, such as the storage of retrieved memoranda in a working memory buffer for further cognitive processing.

Amygdala atrophy affects emotion-related activity in face-responsive regions in frontotemporal degeneration.

PubMed

De Winter, François-Laurent; Van den Stock, Jan; de Gelder, Beatrice; Peeters, Ronald; Jastorff, Jan; Sunaert, Stefan; Vanduffel, Wim; Vandenberghe, Rik; Vandenbulcke, Mathieu

2016-09-01

In the healthy brain, modulatory influences from the amygdala commonly explain enhanced activation in face-responsive areas by emotional facial expressions relative to neutral expressions. In the behavioral variant frontotemporal dementia (bvFTD) facial emotion recognition is impaired and has been associated with atrophy of the amygdala. By combining structural and functional MRI in 19 patients with bvFTD and 20 controls we investigated the neural effects of emotion in face-responsive cortex and its relationship with amygdalar gray matter (GM) volume in neurodegeneration. Voxel-based morphometry revealed decreased GM volume in anterior medio-temporal regions including amygdala in patients compared to controls. During fMRI, we presented dynamic facial expressions (fear and chewing) and their spatiotemporally scrambled versions. We found enhanced activation for fearful compared to neutral faces in ventral temporal cortex and superior temporal sulcus in controls, but not in patients. In the bvFTD group left amygdalar GM volume correlated positively with emotion-related activity in left fusiform face area (FFA). This correlation was amygdala-specific and driven by GM in superficial and basolateral (BLA) subnuclei, consistent with reported amygdalar-cortical networks. The data suggests that anterior medio-temporal atrophy in bvFTD affects emotion processing in distant posterior areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex

PubMed Central

Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S.; Smolka, Michael N.

2014-01-01

Background A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. Methods We measured inhibitory control in fifty young adults with a stop-signal task (SST) during functional magnetic resonance imaging (fMRI). In a single-blind placebo-controlled cross-over design, all participants performed the SST once under alcohol with a breath alcohol concentration (BrAC) of 0.6 g/kg, and once under placebo. In addition, alcohol consumption was assessed using a free-access alcohol self-administration (ASA) paradigm in the same participants. Results Inhibitory control was robustly decreased under alcohol compared to placebo indicated by longer stop-signal reaction times (SSRTs). On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals, and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. Conclusion We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control may enhance alcohol consumption in young adults which might promote future alcohol problems. PMID:24560581

Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex.

PubMed

Gan, Gabriela; Guevara, Alvaro; Marxen, Michael; Neumann, Maike; Jünger, Elisabeth; Kobiella, Andrea; Mennigen, Eva; Pilhatsch, Maximilian; Schwarz, Daniel; Zimmermann, Ulrich S; Smolka, Michael N

2014-11-01

A self-enhancing loop between impaired inhibitory control under alcohol and alcohol consumption has been proposed as a possible mechanism underlying dysfunctional drinking in susceptible people. However, the neural underpinnings of alcohol-induced impairment of inhibitory control are widely unknown. We measured inhibitory control in 50 young adults with a stop-signal task during functional magnetic resonance imaging. In a single-blind placebo-controlled cross-over design, all participants performed the stop-signal task once under alcohol with a breath alcohol concentration of .6 g/kg and once under placebo. In addition, alcohol consumption was assessed with a free-access alcohol self-administration paradigm in the same participants. Inhibitory control was robustly decreased under alcohol compared with placebo, indicated by longer stop-signal reaction times. On the neural level, impaired inhibitory control under alcohol was associated with attenuated brain responses in the right fronto-temporal portion of the inhibition network that supports the attentional capture of infrequent stop-signals and subsequent updating of action plans from response execution to inhibition. Furthermore, the extent of alcohol-induced impairment of inhibitory control predicted free-access alcohol consumption. We suggest that during inhibitory control alcohol affects cognitive processes preceding actual motor inhibition. Under alcohol, decreased brain responses in right fronto-temporal areas might slow down the attentional capture of infrequent stop-signals and subsequent updating of action plans, which leads to impaired inhibitory control. In turn, pronounced alcohol-induced impairment of inhibitory control might enhance alcohol consumption in young adults, which might promote future alcohol problems. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Domain-specific impairment of source memory following a right posterior medial temporal lobe lesion.

PubMed

Peters, Jan; Koch, Benno; Schwarz, Michael; Daum, Irene

2007-01-01

This single case analysis of memory performance in a patient with an ischemic lesion affecting posterior but not anterior right medial temporal lobe (MTL) indicates that source memory can be disrupted in a domain-specific manner. The patient showed normal recognition memory for gray-scale photos of objects (visual condition) and spoken words (auditory condition). While memory for visual source (texture/color of the background against which pictures appeared) was within the normal range, auditory source memory (male/female speaker voice) was at chance level, a performance pattern significantly different from the control group. This dissociation is consistent with recent fMRI evidence of anterior/posterior MTL dissociations depending upon the nature of source information (visual texture/color vs. auditory speaker voice). The findings are in good agreement with the view of dissociable memory processing by the perirhinal cortex (anterior MTL) and parahippocampal cortex (posterior MTL), depending upon the neocortical input that these regions receive. (c) 2007 Wiley-Liss, Inc.

Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections.

PubMed

Barker, Gareth R I; Banks, Paul J; Scott, Hannah; Ralph, G Scott; Mitrophanous, Kyriacos A; Wong, Liang-Fong; Bashir, Zafar I; Uney, James B; Warburton, E Clea

2017-02-01

Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

Mentalising music in frontotemporal dementia

PubMed Central

Downey, Laura E.; Blezat, Alice; Nicholas, Jennifer; Omar, Rohani; Golden, Hannah L.; Mahoney, Colin J.; Crutch, Sebastian J.; Warren, Jason D.

2013-01-01

Despite considerable recent interest, the biological basis and clinical diagnosis of behavioural variant frontotemporal dementia (bvFTD) pose unresolved problems. Mentalising (the cognitive capacity to interpret the behaviour of oneself and others in terms of mental states) is impaired as a prominent feature of bvFTD, consistent with involvement of brain regions including ventro-medial prefrontal cortex (PFC), orbitofrontal cortex and anterior temporal lobes. Here, we investigated mentalising ability in a cohort of patients with bvFTD using a novel modality: music. We constructed a novel neuropsychological battery requiring attribution of affective mental or non-mental associations to musical stimuli. Mentalising performance of patients with bvFTD (n = 20) was assessed in relation to matched healthy control subjects (n = 20); patients also had a comprehensive assessment of behaviour and general neuropsychological functions. Neuroanatomical correlates of performance on the experimental tasks were investigated using voxel-based morphometry of patients' brain magnetic resonance imaging (MRI) scans. Compared to healthy control subjects, patients showed impaired ability to attribute mental states but not non-mental characteristics to music, and this deficit correlated with performance on a standard test of social inference and with carer ratings of patients' empathic capacity, but not with other potentially relevant measures of general neuropsychological function. Mentalising performance in the bvFTD group was associated with grey matter changes in anterior temporal lobe and ventro-medial PFC. These findings suggest that music can represent surrogate mental states and the ability to construct such mental representations is impaired in bvFTD, with potential implications for our understanding of the biology of bvFTD and human social cognition more broadly. PMID:23107380

Auditory Temporal Acuity Probed With Cochlear Implant Stimulation and Cortical Recording

PubMed Central

Kirby, Alana E.

2010-01-01

Cochlear implants stimulate the auditory nerve with amplitude-modulated (AM) electric pulse trains. Pulse rates >2,000 pulses per second (pps) have been hypothesized to enhance transmission of temporal information. Recent studies, however, have shown that higher pulse rates impair phase locking to sinusoidal AM in the auditory cortex and impair perceptual modulation detection. Here, we investigated the effects of high pulse rates on the temporal acuity of transmission of pulse trains to the auditory cortex. In anesthetized guinea pigs, signal-detection analysis was used to measure the thresholds for detection of gaps in pulse trains at rates of 254, 1,017, and 4,069 pps and in acoustic noise. Gap-detection thresholds decreased by an order of magnitude with increases in pulse rate from 254 to 4,069 pps. Such a pulse-rate dependence would likely influence speech reception through clinical speech processors. To elucidate the neural mechanisms of gap detection, we measured recovery from forward masking after a 196.6-ms pulse train. Recovery from masking was faster at higher carrier pulse rates and masking increased linearly with current level. We fit the data with a dual-exponential recovery function, consistent with a peripheral and a more central process. High-rate pulse trains evoked less central masking, possibly due to adaptation of the response in the auditory nerve. Neither gap detection nor forward masking varied with cortical depth, indicating that these processes are likely subcortical. These results indicate that gap detection and modulation detection are mediated by two separate neural mechanisms. PMID:19923242

Retrograde and anterograde memory following selective damage to the dorsolateral entorhinal cortex.

PubMed

Gervais, Nicole J; Barrett-Bernstein, Meagan; Sutherland, Robert J; Mumby, Dave G

2014-12-01

Anatomical and electrophysiological evidence suggest the dorsolateral entorhinal cortex (DLEC) is involved in processing spatial information, but there is currently no consensus on whether its functions are necessary for normal spatial learning and memory. The present study examined the effects of excitotoxic lesions of the DLEC on retrograde and anterograde memory on two tests of allocentric spatial learning: a hidden fixed-platform watermaze task, and a novelty-preference-based dry-maze test. Deficits were observed on both tests when training occurred prior to but not following n-methyl d-aspartate (NMDA) lesions of DLEC, suggesting retrograde memory impairment in the absence of anterograde impairments for the same information. The retrograde memory impairments were temporally-graded; rats that received DLEC lesions 1-3 days following training displayed deficits, while those that received lesions 7-10 days following training performed like a control group that received sham surgery. The deficits were not attenuated by co-infusion of tetrodotoxin, suggesting they are not due to disruption of neural processing in structures efferent to the DLEC, such as the hippocampus. The present findings provide evidence that the DLEC is involved in the consolidation of allocentric spatial information. Copyright © 2014 Elsevier Inc. All rights reserved.

The neural basis for writing from dictation in the temporoparietal cortex.

PubMed

Roux, Franck-Emmanuel; Durand, Jean-Baptiste; Réhault, Emilie; Planton, Samuel; Draper, Louisa; Démonet, Jean-François

2014-01-01

Cortical electrical stimulation mapping was used to study neural substrates of the function of writing in the temporoparietal cortex. We identified the sites involved in oral language (sentence reading and naming) and writing from dictation, in order to spare these areas during removal of brain tumours in 30 patients (23 in the left, and 7 in the right hemisphere). Electrostimulation of the cortex impaired writing ability in 62 restricted cortical areas (.25 cm2). These were found in left temporoparietal lobes and were mostly located along the superior temporal gyrus (Brodmann's areas 22 and 42). Stimulation of right temporoparietal lobes in right-handed patients produced no writing impairments. However there was a high variability of location between individuals. Stimulation resulted in combined symptoms (affecting oral language and writing) in fourteen patients, whereas in eight other patients, stimulation-induced pure agraphia symptoms with no oral language disturbance in twelve of the identified areas. Each detected area affected writing in a different way. We detected the various different stages of the auditory-to-motor pathway of writing from dictation: either through comprehension of the dictated sentences (word deafness areas), lexico-semantic retrieval, or phonologic processing. In group analysis, barycentres of all different types of writing interferences reveal a hierarchical functional organization along the superior temporal gyrus from initial word recognition to lexico-semantic and phonologic processes along the ventral and the dorsal comprehension pathways, supporting the previously described auditory-to-motor process. The left posterior Sylvian region supports different aspects of writing function that are extremely specialized and localized, sometimes being segregated in a way that could account for the occurrence of pure agraphia that has long-been described in cases of damage to this region. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neuromodulatory Effects of Auditory Training and Hearing Aid Use on Audiovisual Speech Perception in Elderly Individuals

PubMed Central

Yu, Luodi; Rao, Aparna; Zhang, Yang; Burton, Philip C.; Rishiq, Dania; Abrams, Harvey

2017-01-01

Although audiovisual (AV) training has been shown to improve overall speech perception in hearing-impaired listeners, there has been a lack of direct brain imaging data to help elucidate the neural networks and neural plasticity associated with hearing aid (HA) use and auditory training targeting speechreading. For this purpose, the current clinical case study reports functional magnetic resonance imaging (fMRI) data from two hearing-impaired patients who were first-time HA users. During the study period, both patients used HAs for 8 weeks; only one received a training program named ReadMyQuipsTM (RMQ) targeting speechreading during the second half of the study period for 4 weeks. Identical fMRI tests were administered at pre-fitting and at the end of the 8 weeks. Regions of interest (ROI) including auditory cortex and visual cortex for uni-sensory processing, and superior temporal sulcus (STS) for AV integration, were identified for each person through independent functional localizer task. The results showed experience-dependent changes involving ROIs of auditory cortex, STS and functional connectivity between uni-sensory ROIs and STS from pretest to posttest in both cases. These data provide initial evidence for the malleable experience-driven cortical functionality for AV speech perception in elderly hearing-impaired people and call for further studies with a much larger subject sample and systematic control to fill in the knowledge gap to understand brain plasticity associated with auditory rehabilitation in the aging population. PMID:28270763

Neuromodulatory Effects of Auditory Training and Hearing Aid Use on Audiovisual Speech Perception in Elderly Individuals.

PubMed

Yu, Luodi; Rao, Aparna; Zhang, Yang; Burton, Philip C; Rishiq, Dania; Abrams, Harvey

2017-01-01

Although audiovisual (AV) training has been shown to improve overall speech perception in hearing-impaired listeners, there has been a lack of direct brain imaging data to help elucidate the neural networks and neural plasticity associated with hearing aid (HA) use and auditory training targeting speechreading. For this purpose, the current clinical case study reports functional magnetic resonance imaging (fMRI) data from two hearing-impaired patients who were first-time HA users. During the study period, both patients used HAs for 8 weeks; only one received a training program named ReadMyQuips TM (RMQ) targeting speechreading during the second half of the study period for 4 weeks. Identical fMRI tests were administered at pre-fitting and at the end of the 8 weeks. Regions of interest (ROI) including auditory cortex and visual cortex for uni-sensory processing, and superior temporal sulcus (STS) for AV integration, were identified for each person through independent functional localizer task. The results showed experience-dependent changes involving ROIs of auditory cortex, STS and functional connectivity between uni-sensory ROIs and STS from pretest to posttest in both cases. These data provide initial evidence for the malleable experience-driven cortical functionality for AV speech perception in elderly hearing-impaired people and call for further studies with a much larger subject sample and systematic control to fill in the knowledge gap to understand brain plasticity associated with auditory rehabilitation in the aging population.

Mild Perceptual Categorization Deficits Follow Bilateral Removal of Anterior Inferior Temporal Cortex in Rhesus Monkeys.

PubMed

Matsumoto, Narihisa; Eldridge, Mark A G; Saunders, Richard C; Reoli, Rachel; Richmond, Barry J

2016-01-06

In primates, visual recognition of complex objects depends on the inferior temporal lobe. By extension, categorizing visual stimuli based on similarity ought to depend on the integrity of the same area. We tested three monkeys before and after bilateral anterior inferior temporal cortex (area TE) removal. Although mildly impaired after the removals, they retained the ability to assign stimuli to previously learned categories, e.g., cats versus dogs, and human versus monkey faces, even with trial-unique exemplars. After the TE removals, they learned in one session to classify members from a new pair of categories, cars versus trucks, as quickly as they had learned the cats versus dogs before the removals. As with the dogs and cats, they generalized across trial-unique exemplars of cars and trucks. However, as seen in earlier studies, these monkeys with TE removals had difficulty learning to discriminate between two simple black and white stimuli. These results raise the possibility that TE is needed for memory of simple conjunctions of basic features, but that it plays only a small role in generalizing overall configural similarity across a large set of stimuli, such as would be needed for perceptual categorical assignment. The process of seeing and recognizing objects is attributed to a set of sequentially connected brain regions stretching forward from the primary visual cortex through the temporal lobe to the anterior inferior temporal cortex, a region designated area TE. Area TE is considered the final stage for recognizing complex visual objects, e.g., faces. It has been assumed, but not tested directly, that this area would be critical for visual generalization, i.e., the ability to place objects such as cats and dogs into their correct categories. Here, we demonstrate that monkeys rapidly and seemingly effortlessly categorize large sets of complex images (cats vs dogs, cars vs trucks), surprisingly, even after removal of area TE, leaving a puzzle about how this generalization is done. Copyright © 2016 the authors 0270-6474/16/360043-11$15.00/0.

Combined diffusion-weighted and functional magnetic resonance imaging reveals a temporal-occipital network involved in auditory-visual object processing

PubMed Central

Beer, Anton L.; Plank, Tina; Meyer, Georg; Greenlee, Mark W.

2013-01-01

Functional magnetic resonance imaging (MRI) showed that the superior temporal and occipital cortex are involved in multisensory integration. Probabilistic fiber tracking based on diffusion-weighted MRI suggests that multisensory processing is supported by white matter connections between auditory cortex and the temporal and occipital lobe. Here, we present a combined functional MRI and probabilistic fiber tracking study that reveals multisensory processing mechanisms that remained undetected by either technique alone. Ten healthy participants passively observed visually presented lip or body movements, heard speech or body action sounds, or were exposed to a combination of both. Bimodal stimulation engaged a temporal-occipital brain network including the multisensory superior temporal sulcus (msSTS), the lateral superior temporal gyrus (lSTG), and the extrastriate body area (EBA). A region-of-interest (ROI) analysis showed multisensory interactions (e.g., subadditive responses to bimodal compared to unimodal stimuli) in the msSTS, the lSTG, and the EBA region. Moreover, sounds elicited responses in the medial occipital cortex. Probabilistic tracking revealed white matter tracts between the auditory cortex and the medial occipital cortex, the inferior occipital cortex (IOC), and the superior temporal sulcus (STS). However, STS terminations of auditory cortex tracts showed limited overlap with the msSTS region. Instead, msSTS was connected to primary sensory regions via intermediate nodes in the temporal and occipital cortex. Similarly, the lSTG and EBA regions showed limited direct white matter connections but instead were connected via intermediate nodes. Our results suggest that multisensory processing in the STS is mediated by separate brain areas that form a distinct network in the lateral temporal and inferior occipital cortex. PMID:23407860

Neural circuitry of emotional face processing in autism spectrum disorders.

PubMed

Monk, Christopher S; Weng, Shih-Jen; Wiggins, Jillian Lee; Kurapati, Nikhil; Louro, Hugo M C; Carrasco, Melisa; Maslowsky, Julie; Risi, Susan; Lord, Catherine

2010-03-01

Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces. Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces. In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces. The small sample size may have affected our ability to detect additional group differences. When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.

Damage to temporo-parietal cortex decreases incidental activation of thematic relations during spoken word comprehension

PubMed Central

Mirman, Daniel; Graziano, Kristen M.

2012-01-01

Both taxonomic and thematic semantic relations have been studied extensively in behavioral studies and there is an emerging consensus that the anterior temporal lobe plays a particularly important role in the representation and processing of taxonomic relations, but the neural basis of thematic semantics is less clear. We used eye tracking to examine incidental activation of taxonomic and thematic relations during spoken word comprehension in participants with aphasia. Three groups of participants were tested: neurologically intact control participants (N=14), individuals with aphasia resulting from lesions in left hemisphere BA 39 and surrounding temporo-parietal cortex regions (N=7), and individuals with the same degree of aphasia severity and semantic impairment and anterior left hemisphere lesions (primarily inferior frontal gyrus and anterior temporal lobe) that spared BA 39 (N=6). The posterior lesion group showed reduced and delayed activation of thematic relations, but not taxonomic relations. In contrast, the anterior lesion group exhibited longer-lasting activation of taxonomic relations and did not differ from control participants in terms of activation of thematic relations. These results suggest that taxonomic and thematic semantic knowledge are functionally and neuroanatomically distinct, with the temporo-parietal cortex playing a particularly important role in thematic semantics. PMID:22571932

Network modulation during complex syntactic processing

PubMed Central

den Ouden, Dirk-Bart; Saur, Dorothee; Mader, Wolfgang; Schelter, Björn; Lukic, Sladjana; Wali, Eisha; Timmer, Jens; Thompson, Cynthia K.

2011-01-01

Complex sentence processing is supported by a left-lateralized neural network including inferior frontal cortex and posterior superior temporal cortex. This study investigates the pattern of connectivity and information flow within this network. We used fMRI BOLD data derived from 12 healthy participants reported in an earlier study (Thompson, C. K., Den Ouden, D. B., Bonakdarpour, B., Garibaldi, K., & Parrish, T. B. (2010b). Neural plasticity and treatment-induced recovery of sentence processing in agrammatism. Neuropsychologia, 48(11), 3211-3227) to identify activation peaks associated with object-cleft over syntactically less complex subject-cleft processing. Directed Partial Correlation Analysis was conducted on time series extracted from participant-specific activation peaks and showed evidence of functional connectivity between four regions, linearly between premotor cortex, inferior frontal gyrus, posterior superior temporal sulcus and anterior middle temporal gyrus. This pattern served as the basis for Dynamic Causal Modeling of networks with a driving input to posterior superior temporal cortex, which likely supports thematic role assignment, and networks with a driving input to inferior frontal cortex, a core region associated with syntactic computation. The optimal model was determined through both frequentist and Bayesian model selection and turned out to reflect a network with a primary drive from inferior frontal cortex and modulation of the connection between inferior frontal and posterior superior temporal cortex by complex sentence processing. The winning model also showed a substantive role for a feedback mechanism from posterior superior temporal cortex back to inferior frontal cortex. We suggest that complex syntactic processing is driven by word-order analysis, supported by inferior frontal cortex, in an interactive relation with posterior superior temporal cortex, which supports verb argument structure processing. PMID:21820518

Brain regions sensitive to the face inversion effect: a functional magnetic resonance imaging study in humans.

PubMed

Leube, Dirk T; Yoon, Hyo Woon; Rapp, Alexander; Erb, Michael; Grodd, Wolfgang; Bartels, Mathias; Kircher, Tilo T J

2003-05-22

Perception of upright faces relies on configural processing. Therefore recognition of inverted, compared to upright faces is impaired. In a functional magnetic resonance imaging experiment we investigated the neural correlate of a face inversion task. Thirteen healthy subjects were presented with a equal number of upright and inverted faces alternating with a low level baseline with an upright and inverted picture of an abstract symbol. Brain activation was calculated for upright minus inverted faces. For this differential contrast, we found a signal change in the right superior temporal sulcus and right insula. Configural properties are processed in a network comprising right superior temporal and insular cortex.

Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of structure, integrity, and connectivity.

PubMed

Keller, Simon S; O'Muircheartaigh, Jonathan; Traynor, Catherine; Towgood, Karren; Barker, Gareth J; Richardson, Mark P

2014-02-01

Thalamic abnormality in temporal lobe epilepsy (TLE) is well known from imaging studies, but evidence is lacking regarding connectivity profiles of the thalamus and their involvement in the disease process. We used a novel multisequence magnetic resonance imaging (MRI) protocol to elucidate the relationship between mesial temporal and thalamic pathology in TLE. For 23 patients with TLE and 23 healthy controls, we performed T1 -weighted (for analysis of tissue structure), diffusion tensor imaging (tissue connectivity), and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used connectivity-based segmentation to determine connectivity patterns of thalamus to ipsilateral cortical regions (occipital, parietal, prefrontal, postcentral, precentral, and temporal). We subsequently determined volumes, mean tractography streamlines, and mean T1 and T2 relaxometry values for each thalamic segment preferentially connecting to a given cortical region, and of the hippocampus and entorhinal cortex. As expected, patients had significant volume reduction and increased T2 relaxation time in ipsilateral hippocampus and entorhinal cortex. There was bilateral volume loss, mean streamline reduction, and T2 increase of the thalamic segment preferentially connected to temporal lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with no evidence of significant change in any other thalamic segments. Left and right thalamotemporal segment volume and T2 were significantly correlated with volume and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic), mesial temporal structures. These convergent and robust data indicate that thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected to the epileptogenic temporal lobe. The degree of thalamic pathology is related to the extent of mesial temporal lobe damage in TLE. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Temporal kinetics of prefrontal modulation of the extrastriate cortex during visual attention.

PubMed

Yago, Elena; Duarte, Audrey; Wong, Ting; Barceló, Francisco; Knight, Robert T

2004-12-01

Single-unit, event-related potential (ERP), and neuroimaging studies have implicated the prefrontal cortex (PFC) in top-down control of attention and working memory. We conducted an experiment in patients with unilateral PFC damage (n = 8) to assess the temporal kinetics of PFC-extrastriate interactions during visual attention. Subjects alternated attention between the left and the right hemifields in successive runs while they detected target stimuli embedded in streams of repetitive task-irrelevant stimuli (standards). The design enabled us to examine tonic (spatial selection) and phasic (feature selection) PFC-extrastriate interactions. PFC damage impaired performance in the visual field contralateral to lesions, as manifested by both larger reaction times and error rates. Assessment of the extrastriate P1 ERP revealed that the PFC exerts a tonic (spatial selection) excitatory input to the ipsilateral extrastriate cortex as early as 100 msec post stimulus delivery. The PFC exerts a second phasic (feature selection) excitatory extrastriate modulation from 180 to 300 msec, as evidenced by reductions in selection negativity after damage. Finally, reductions of the N2 ERP to target stimuli supports the notion that the PFC exerts a third phasic (target selection) signal necessary for successful template matching during postselection analysis of target features. The results provide electrophysiological evidence of three distinct tonic and phasic PFC inputs to the extrastriate cortex in the initial few hundred milliseconds of stimulus processing. Damage to this network appears to underlie the pervasive deficits in attention observed in patients with prefrontal lesions.

Entorhinal Cortex: Antemortem Cortical Thickness and Postmortem Neurofibrillary Tangles and Amyloid Pathology.

PubMed

Thaker, A A; Weinberg, B D; Dillon, W P; Hess, C P; Cabral, H J; Fleischman, D A; Leurgans, S E; Bennett, D A; Hyman, B T; Albert, M S; Killiany, R J; Fischl, B; Dale, A M; Desikan, R S

2017-05-01

The entorhinal cortex, a critical gateway between the neocortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the entorhinal cortex, whether antemortem entorhinal cortex thickness is associated with postmortem tangle burden within the entorhinal cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of entorhinal cortex thickness and postmortem neuropathological measures. We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the entorhinal cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between entorhinal cortex thickness and tangles and amyloid-β load within the entorhinal cortex and medial temporal and neocortical regions. We found a significant relationship between antemortem entorhinal cortex thickness and entorhinal cortex ( P = .006) and medial temporal lobe tangles ( P = .002); we found no relationship between entorhinal cortex thickness and entorhinal cortex ( P = .09) and medial temporal lobe amyloid-β ( P = .09). We also found a significant association between entorhinal cortex thickness and cortical tangles ( P = .003) and amyloid-β ( P = .01). We found no relationship between parahippocampal gyrus thickness and entorhinal cortex ( P = .31) and medial temporal lobe tangles ( P = .051). Our findings indicate that entorhinal cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology. © 2017 by American Journal of Neuroradiology.

Cortical activation during Braille reading is influenced by early visual experience in subjects with severe visual disability: a correlational fMRI study.

PubMed

Melzer, P; Morgan, V L; Pickens, D R; Price, R R; Wall, R S; Ebner, F F

2001-11-01

Functional magnetic resonance imaging was performed on blind adults resting and reading Braille. The strongest activation was found in primary somatic sensory/motor cortex on both cortical hemispheres. Additional foci of activation were situated in the parietal, temporal, and occipital lobes where visual information is processed in sighted persons. The regions were differentiated most in the correlation of their time courses of activation with resting and reading. Differences in magnitude and expanse of activation were substantially less significant. Among the traditionally visual areas, the strength of correlation was greatest in posterior parietal cortex and moderate in occipitotemporal, lateral occipital, and primary visual cortex. It was low in secondary visual cortex as well as in dorsal and ventral inferior temporal cortex and posterior middle temporal cortex. Visual experience increased the strength of correlation in all regions except dorsal inferior temporal and posterior parietal cortex. The greatest statistically significant increase, i.e., approximately 30%, was in ventral inferior temporal and posterior middle temporal cortex. In these regions, words are analyzed semantically, which may be facilitated by visual experience. In contrast, visual experience resulted in a slight, insignificant diminution of the strength of correlation in dorsal inferior temporal cortex where language is analyzed phonetically. These findings affirm that posterior temporal regions are engaged in the processing of written language. Moreover, they suggest that this function is modified by early visual experience. Furthermore, visual experience significantly strengthened the correlation of activation and Braille reading in occipital regions traditionally involved in the processing of visual features and object recognition suggesting a role for visual imagery. Copyright 2001 Wiley-Liss, Inc.

Mentalising music in frontotemporal dementia.

PubMed

Downey, Laura E; Blezat, Alice; Nicholas, Jennifer; Omar, Rohani; Golden, Hannah L; Mahoney, Colin J; Crutch, Sebastian J; Warren, Jason D

2013-01-01

Despite considerable recent interest, the biological basis and clinical diagnosis of behavioural variant frontotemporal dementia (bvFTD) pose unresolved problems. Mentalising (the cognitive capacity to interpret the behaviour of oneself and others in terms of mental states) is impaired as a prominent feature of bvFTD, consistent with involvement of brain regions including ventro-medial prefrontal cortex (PFC), orbitofrontal cortex and anterior temporal lobes. Here, we investigated mentalising ability in a cohort of patients with bvFTD using a novel modality: music. We constructed a novel neuropsychological battery requiring attribution of affective mental or non-mental associations to musical stimuli. Mentalising performance of patients with bvFTD (n = 20) was assessed in relation to matched healthy control subjects (n = 20); patients also had a comprehensive assessment of behaviour and general neuropsychological functions. Neuroanatomical correlates of performance on the experimental tasks were investigated using voxel-based morphometry of patients' brain magnetic resonance imaging (MRI) scans. Compared to healthy control subjects, patients showed impaired ability to attribute mental states but not non-mental characteristics to music, and this deficit correlated with performance on a standard test of social inference and with carer ratings of patients' empathic capacity, but not with other potentially relevant measures of general neuropsychological function. Mentalising performance in the bvFTD group was associated with grey matter changes in anterior temporal lobe and ventro-medial PFC. These findings suggest that music can represent surrogate mental states and the ability to construct such mental representations is impaired in bvFTD, with potential implications for our understanding of the biology of bvFTD and human social cognition more broadly. Copyright © 2012 Elsevier Ltd. All rights reserved.

Involvement of the prelimbic cortex in contextual fear conditioning with temporal and spatial discontinuity.

PubMed

Santos, Thays Brenner; Kramer-Soares, Juliana Carlota; Favaro, Vanessa Manchim; Oliveira, Maria Gabriela Menezes

2017-10-01

Time plays an important role in conditioning, it is not only possible to associate stimuli with events that overlap, as in delay fear conditioning, but it is also possible to associate stimuli that are discontinuous in time, as shown in trace conditioning for a discrete stimuli. The environment itself can be a powerful conditioned stimulus (CS) and be associated to unconditioned stimulus (US). Thus, the aim of the present study was to determine the parameters in which contextual fear conditioning occurs by the maintenance of a contextual representation over short and long time intervals. The results showed that a contextual representation can be maintained and associated after 5s, even in the absence of a 15s re-exposure to the training context before US delivery. The same effect was not observed with a 24h interval of discontinuity. Furthermore, optimal conditioned response with a 5s interval is produced only when the contexts (of pre-exposure and shock) match. As the pre-limbic cortex (PL) is necessary for the maintenance of a continuous representation of a stimulus, the involvement of the PL in this temporal and contextual processing was investigated. The reversible inactivation of the PL by muscimol infusion impaired the acquisition of contextual fear conditioning with a 5s interval, but not with a 24h interval, and did not impair delay fear conditioning. The data provided evidence that short and long intervals of discontinuity have different mechanisms, thus contributing to a better understanding of PL involvement in contextual fear conditioning and providing a model that considers both temporal and contextual factors in fear conditioning. Copyright © 2017 Elsevier Inc. All rights reserved.

Medial temporal and neocortical contributions to remote memory for semantic narratives: evidence from amnesia.

PubMed

Verfaellie, Mieke; Bousquet, Kathryn; Keane, Margaret M

2014-08-01

Studies of remote memory for semantic facts and concepts suggest that hippocampal lesions lead to a temporally graded impairment that extends no more than ten years prior to the onset of amnesia. Such findings have led to the notion that once consolidated, semantic memories are represented neocortically and are no longer dependent on the hippocampus. Here, we examined the fate of well-established semantic narratives following medial temporal lobe (MTL) lesions. Seven amnesic patients, five with lesions restricted to the MTL and two with lesions extending into lateral temporal cortex (MTL+), were asked to recount fairy tales and bible stories that they rated as familiar. Narratives were scored for number and type of details, number of main thematic elements, and order in which the main thematic elements were recounted. In comparison to controls, patients with MTL lesions produced fewer details, but the number and order of main thematic elements generated was intact. By contrast, patients with MTL+ lesions showed a pervasive impairment, affecting not only the generation of details, but also the generation and ordering of main steps. These findings challenge the notion that, once consolidated, semantic memories are no longer dependent on the hippocampus for retrieval. Possible hippocampal contributions to the retrieval of detailed semantic narratives are discussed. Published by Elsevier Ltd.

Cognitive neuropsychological analysis and neuroanatomic correlates in a case of acute anomia.

PubMed

Raymer, A M; Foundas, A L; Maher, L M; Greenwald, M L; Morris, M; Rothi, L J; Heilman, K M

1997-06-01

We describe an analysis of lexical processing performed in a patient with the acute onset of an isolated anomia. Based on a model of lexical processing, we evaluated hypotheses as to the source of the naming deficit. We observed impairments in oral and written picture naming and oral naming to definition with relatively intact semantic processing across input modalities, suggesting that output from the semantic system was impaired. In contrast to previous reports, we propose that this pattern represents an impairment that arises late in semantic processing prior to accessing mode-specific verbal and graphemic output lexicons. These deficits were associated with a lesion in the posterior portion of the middle temporal gyrus or area 37, an area of supramodal association cortex that is uniquely suited as a substrate for the multimodal deficit in naming.

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

PubMed Central

Robson, Holly; Zahn, Roland; Keidel, James L.; Binney, Richard J.; Sage, Karen; Lambon Ralph, Matthew A.

2014-01-01

Wernicke’s aphasia occurs after a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory–verbal comprehension is significantly impaired in Wernicke’s aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used functional magnetic resonance imaging to investigate the neural basis of written word and picture semantic processing in Wernicke’s aphasia, with the wider aim of examining how the semantic system is altered after damage to the classical comprehension regions. Twelve participants with chronic Wernicke’s aphasia and 12 control participants performed semantic animate–inanimate judgements and a visual height judgement baseline task. Whole brain and region of interest analysis in Wernicke’s aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke’s aphasia group displayed an ‘over-activation’ in comparison with control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke’s aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results provide support for models in which the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions. PMID:24519979

The anterior temporal lobes support residual comprehension in Wernicke's aphasia.

PubMed

Robson, Holly; Zahn, Roland; Keidel, James L; Binney, Richard J; Sage, Karen; Lambon Ralph, Matthew A

2014-03-01

Wernicke's aphasia occurs after a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke's aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used functional magnetic resonance imaging to investigate the neural basis of written word and picture semantic processing in Wernicke's aphasia, with the wider aim of examining how the semantic system is altered after damage to the classical comprehension regions. Twelve participants with chronic Wernicke's aphasia and 12 control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and region of interest analysis in Wernicke's aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke's aphasia group displayed an 'over-activation' in comparison with control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke's aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results provide support for models in which the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions.

Old Brains Come Uncoupled in Sleep: Slow Wave-Spindle Synchrony, Brain Atrophy, and Forgetting.

PubMed

Helfrich, Randolph F; Mander, Bryce A; Jagust, William J; Knight, Robert T; Walker, Matthew P

2018-01-03

The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Cross-language differences in the brain network subserving intelligible speech.

PubMed

Ge, Jianqiao; Peng, Gang; Lyu, Bingjiang; Wang, Yi; Zhuo, Yan; Niu, Zhendong; Tan, Li Hai; Leff, Alexander P; Gao, Jia-Hong

2015-03-10

How is language processed in the brain by native speakers of different languages? Is there one brain system for all languages or are different languages subserved by different brain systems? The first view emphasizes commonality, whereas the second emphasizes specificity. We investigated the cortical dynamics involved in processing two very diverse languages: a tonal language (Chinese) and a nontonal language (English). We used functional MRI and dynamic causal modeling analysis to compute and compare brain network models exhaustively with all possible connections among nodes of language regions in temporal and frontal cortex and found that the information flow from the posterior to anterior portions of the temporal cortex was commonly shared by Chinese and English speakers during speech comprehension, whereas the inferior frontal gyrus received neural signals from the left posterior portion of the temporal cortex in English speakers and from the bilateral anterior portion of the temporal cortex in Chinese speakers. Our results revealed that, although speech processing is largely carried out in the common left hemisphere classical language areas (Broca's and Wernicke's areas) and anterior temporal cortex, speech comprehension across different language groups depends on how these brain regions interact with each other. Moreover, the right anterior temporal cortex, which is crucial for tone processing, is equally important as its left homolog, the left anterior temporal cortex, in modulating the cortical dynamics in tone language comprehension. The current study pinpoints the importance of the bilateral anterior temporal cortex in language comprehension that is downplayed or even ignored by popular contemporary models of speech comprehension.

Cross-language differences in the brain network subserving intelligible speech

PubMed Central

Ge, Jianqiao; Peng, Gang; Lyu, Bingjiang; Wang, Yi; Zhuo, Yan; Niu, Zhendong; Tan, Li Hai; Leff, Alexander P.; Gao, Jia-Hong

2015-01-01

How is language processed in the brain by native speakers of different languages? Is there one brain system for all languages or are different languages subserved by different brain systems? The first view emphasizes commonality, whereas the second emphasizes specificity. We investigated the cortical dynamics involved in processing two very diverse languages: a tonal language (Chinese) and a nontonal language (English). We used functional MRI and dynamic causal modeling analysis to compute and compare brain network models exhaustively with all possible connections among nodes of language regions in temporal and frontal cortex and found that the information flow from the posterior to anterior portions of the temporal cortex was commonly shared by Chinese and English speakers during speech comprehension, whereas the inferior frontal gyrus received neural signals from the left posterior portion of the temporal cortex in English speakers and from the bilateral anterior portion of the temporal cortex in Chinese speakers. Our results revealed that, although speech processing is largely carried out in the common left hemisphere classical language areas (Broca’s and Wernicke’s areas) and anterior temporal cortex, speech comprehension across different language groups depends on how these brain regions interact with each other. Moreover, the right anterior temporal cortex, which is crucial for tone processing, is equally important as its left homolog, the left anterior temporal cortex, in modulating the cortical dynamics in tone language comprehension. The current study pinpoints the importance of the bilateral anterior temporal cortex in language comprehension that is downplayed or even ignored by popular contemporary models of speech comprehension. PMID:25713366

Evidence of an amnesia-like cued-recall memory impairment in nondementing idiopathic Parkinson's disease.

PubMed

Edelstyn, Nicola M J; John, Christopher M; Shepherd, Thomas A; Drakeford, Justine L; Clark-Carter, David; Ellis, Simon J; Mayes, Andrew R

2015-10-01

Medicated, non-dementing mild-to-moderate Parkinson's disease (PD) patients usually show recall/recollection impairments but have only occasionally shown familiarity impairments. We aimed to assess two explanations of this pattern of impairment. Recollection typically improves when effortful planning of encoding and retrieval processing is engaged. This depends on prefrontally-dependent executive processes, which are often disrupted in PD. Relative to an unguided encoding and retrieval of words condition (C1), giving suitable guidance at encoding alone (C2) or at encoding and retrieval (C3) should, if executive processes are disrupted, improve PD recollection more than control recollection and perhaps raise it to normal levels. Familiarity, being a relatively automatic kind of memory, whether impaired or intact, should be unaffected by guidance. According to the second explanation, PD deficits are amnesia-like and caused by medial temporal lobe dysfunction and although poorer recollection, which is caused by hippocampal disruption, may be improved by guidance, it should not improve more than control recollection. Familiarity impairment will also occur if the perirhinal cortex is disrupted, but will be unimproved by guidance. Without guidance, recollection/recall was impaired in thirty PD patients relative to twenty-two healthy controls and remained relatively equally impaired when full guidance was provided (C1 vs C3), both groups improving to broadly the same extent. Although impaired, and markedly less so than recollection, familiarity was not improved by guidance in both groups. The patients showed elevated rates of subclinical depressive symptoms, which weakly correlated with recall/recollection in all three conditions. PD executive function was also deficient and correlated with unguided/C1 recollection only. Our results are consistent with a major cause of the patients' recall/recollection impairments being hippocampal disruption, probably exacerbated by subclinical depressive symptoms. However, the results do not exclude a lesser prefrontal cortex contribution because patient executive functions were impaired and correlated solely with unguided overall recollection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Face processing in different brain areas, and critical band masking.

PubMed

Rolls, Edmund T

2008-09-01

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size, view, and spatial frequency of faces and objects, and that these neurons show rapid processing and rapid learning. Critical band spatial frequency masking is shown to be a property of these face-selective neurons and of the human visual perception of faces. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximizing the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalization, and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses generalize to other views of the same face. A theory is described of how such invariant representations may be produced by self-organizing learning in a hierarchically organized set of visual cortical areas with convergent connectivity. The theory utilizes either temporal or spatial continuity with an associative synaptic modification rule. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye-gaze, face view, and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour. Outputs of these systems reach the amygdala, in which face-selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the human orbitofrontal and pregenual cingulate cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.

The representation of information about faces in the temporal and frontal lobes.

PubMed

Rolls, Edmund T

2007-01-07

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size and view of faces and objects, and that these neurons show rapid processing and rapid learning. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximising the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalisation and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses, generalise to other views of the same face. A theory is described of how such invariant representations may be produced in a hierarchically organised set of visual cortical areas with convergent connectivity. The theory proposes that neurons in these visual areas use a modified Hebb synaptic modification rule with a short-term memory trace to capture whatever can be captured at each stage that is invariant about objects as the objects change in retinal view, position, size and rotation. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye gaze, face view and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour. Outputs of these systems reach the amygdala, in which face-selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the orbitofrontal cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.

Awake craniotomy for tumor resection.

PubMed

Attari, Mohammadali; Salimi, Sohrab

2013-01-01

Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

Awake craniotomy for tumor resection

PubMed Central

Attari, Mohammadali; Salimi, Sohrab

2013-01-01

Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit. PMID:24223378

Prefrontal Cortex and Impulsive Decision Making

PubMed Central

Kim, Soyoun; Lee, Daeyeol

2010-01-01

Impulsivity refers to a set of heterogeneous behaviors that are tuned suboptimally along certain temporal dimensions. Impulsive inter-temporal choice refers to the tendency to forego a large but delayed reward and to seek an inferior but more immediate reward, whereas impulsive motor responses also result when the subjects fail to suppress inappropriate automatic behaviors. In addition, impulsive actions can be produced when too much emphasis is placed on speed rather than accuracy in a wide range of behaviors, including perceptual decision making. Despite this heterogeneous nature, the prefrontal cortex and its connected areas, such as the basal ganglia, play an important role in gating impulsive actions in a variety of behavioral tasks. Here, we describe key features of computations necessary for optimal decision making, and how their failures can lead to impulsive behaviors. We also review the recent findings from neuroimaging and single-neuron recording studies on the neural mechanisms related to impulsive behaviors. Converging approaches in economics, psychology, and neuroscience provide a unique vista for better understanding the nature of behavioral impairments associated with impulsivity. PMID:20728878

Verbal Memory Deficits Are Correlated with Prefrontal Hypometabolism in 18FDG PET of Recreational MDMA Users

PubMed Central

Bosch, Oliver G.; Wagner, Michael; Jessen, Frank; Kühn, Kai-Uwe; Joe, Alexius; Seifritz, Erich; Maier, Wolfgang; Biersack, Hans-Jürgen; Quednow, Boris B.

2013-01-01

Introduction 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users. Methods Brain glucose metabolism in rest was assessed using 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18FDG PET) in 19 male recreational users of MDMA and 19 male drug-naïve controls. 18FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test. Results As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei) of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex. Conclusions Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users arise from combined fronto-parieto-mediotemporal dysfunction. PMID:23585882

Neural foundations to moral reasoning and antisocial behavior

PubMed Central

Yang, Yaling

2006-01-01

A common feature of the antisocial, rule-breaking behavior that is central to criminal, violent and psychopathic individuals is the failure to follow moral guidelines. This review summarizes key findings from brain imaging research on both antisocial behavior and moral reasoning, and integrates these findings into a neural moral model of antisocial behavior. Key areas found to be functionally or structurally impaired in antisocial populations include dorsal and ventral regions of the prefrontal cortex (PFC), amygdala, hippocampus, angular gyrus, anterior cingulate and temporal cortex. Regions most commonly activated in moral judgment tasks consist of the polar/medial and ventral PFC, amygdala, angular gyrus and posterior cingulate. It is hypothesized that the rule-breaking behavior common to antisocial, violent and psychopathic individuals is in part due to impairments in some of the structures (dorsal and ventral PFC, amygdala and angular gyrus) subserving moral cognition and emotion. Impairments to the emotional component that comprises the feeling of what is moral is viewed as the primary deficit in antisocials, although some disruption to the cognitive and cognitive-emotional components of morality (particularly self-referential thinking and emotion regulation) cannot be ruled out. While this neurobiological predisposition is likely only one of several biosocial processes involved in the etiology of antisocial behavior, it raises significant moral issues for the legal system and neuroethics. PMID:18985107

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders.

PubMed

Sato, Wataru; Toichi, Motomi; Uono, Shota; Kochiyama, Takanori

2012-08-13

Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Cognitive Enhancement Therapy Improves Resting-State Functional Connectivity in Early Course Schizophrenia

PubMed Central

Eack, Shaun M.; Newhill, Christina E.; Keshavan, Matcheri S.

2016-01-01

Objective Cognitive remediation is emerging as an effective psychosocial intervention for addressing untreated cognitive and functional impairments in persons with schizophrenia, and might achieve its benefits through neuroplastic changes in brain connectivity. This study seeks to examine the effects of cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a randomized controlled trial with individuals in the early course of schizophrenia. Method Stabilized, early course outpatients with schizophrenia or schizoaffective disorder (N = 41) were randomly assigned to CET (n = 25) or an active enriched supportive therapy (EST) control (n = 16) and treated for 2 years. Functional MRI data were collected annually, and pseudo resting-state functional connectivity analysis was used to examine differential changes in fronto-temporal connectivity between those treated with CET compared with EST. Results Individuals receiving CET evidenced significantly less functional connectivity loss between the resting-state network and the left dorsolateral prefrontal cortex as well as significantly increased connectivity with the right insular cortex compared to EST (all corrected p < .01). These neural networks are involved in emotion processing and problem-solving. Increased connectivity with the right insula significantly mediated CET effects on improved emotion perception (z′ = −1.96, p = .021), and increased connectivity with the left dorsolateral prefrontal cortex mediated CET-related improvements in emotion regulation (z′ = −1.71, p = .052). Conclusions These findings provide preliminary evidence that CET, a psychosocial cognitive remediation intervention, may enhance connectivity between frontal and temporal brain regions implicated in problem-solving and emotion processing in service of cognitive enhancement in schizophrenia. PMID:27713804

Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study.

PubMed

Uhrig, Stefanie; Hirth, Natalie; Broccoli, Laura; von Wilmsdorff, Martina; Bauer, Manfred; Sommer, Clemens; Zink, Mathias; Steiner, Johann; Frodl, Thomas; Malchow, Berend; Falkai, Peter; Spanagel, Rainer; Hansson, Anita C; Schmitt, Andrea

2016-11-01

Schizophrenia is a severe neuropsychiatric disorder with impairments in social cognition. Several brain regions have been implicated in social cognition, including the nucleus caudatus, prefrontal and temporal cortex, and cerebellum. Oxytocin is a critical modulator of social cognition and the formation and maintenance of social relationships and was shown to improve symptoms and social cognition in schizophrenia patients. However, it is unknown whether the oxytocin receptor is altered in the brain. Therefore, we used qRT-PCR and Ornithine Vasotocin Analog ([ 125 I]OVTA)-based receptor autoradiography to investigate oxytocin receptor expression at both the mRNA and protein level in the left prefrontal and middle temporal cortex, left nucleus caudatus, and right posterior superior vermis in 10 schizophrenia patients and 6 healthy controls. Furthermore, to investigate confounding effects of long-term antipsychotic medication we treated rats with clozapine or haloperidol for 12weeks and assessed expression of the oxytocin receptor in cortical and subcortical brain regions. In schizophrenia patients, we found a downregulation of oxytocin receptor mRNA in the temporal cortex and a decrease in receptor binding in the vermis. In the other regions, the results showed trends in the same direction, without reaching statistical significance. We found no differences between antipsychotic-treated rats and controls. Downregulated expression and binding of the oxytocin receptor in brain regions involved in social cognition may lead to a dysfunction of oxytocin signaling. Our results support a dysfunction of the oxytocin receptor in schizophrenia, which may contribute to deficits of social cognition. Copyright © 2016 Elsevier B.V. All rights reserved.

Postencephalitic focal retrograde amnesia after bilateral anterior temporal lobe damage.

PubMed

Tanaka, Y; Miyazawa, Y; Hashimoto, R; Nakano, I; Obayashi, T

1999-07-22

Marked retrograde amnesia with no or almost no anterograde amnesia is rare. Recently, a combination of ventrolateral prefrontal and temporopolar cortical lesions has been suggested as the cause of such isolated or focal retrograde amnesia. It is also assumed that when the right-sided cortical structures are damaged, autobiographical episodic memories are affected. To search for new anatomic substrates for focal retrograde amnesia. We performed extensive neuropsychological tests and obtained detailed neuroimages on a 43-year-old woman who showed a severe, persistent retrograde amnesia but only a limited anterograde amnesia after probable herpes simplex encephalitis. Tests of autobiographical memory revealed that she had a memory loss extending back to her childhood for both semantics and incidents; however, the ability to recall specific episodes appeared much more severely impaired than the ability to recall factual information about her past. The patient also showed profound impairments in recalling public memories; however, her scores improved nearly to a control level on forced-choice recognition memory tasks, although the recall of memories for a decade just before her illness remained mildly impaired. MRI revealed focal pathologies in the temporal poles and the anterior parts of the inferotemporal lobes on both sides, predominantly on the left, with some extension to the anterior parts of the medial temporal lobes. There was additional damage to the left insular cortex and its surrounding structures but no evidence of frontal lobe damage on MRIs or cognitive tests. A profound retrograde amnesia may be produced by damage to the bilateral temporal poles and anterior inferotemporal lobes in the absence of frontal lobe pathologies, and a dense and persistent episodic old memory loss can arise even with a relatively small lesion in the right anterior temporal lobe if it is combined with extensive damage to the left.

Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain.

PubMed

Reinhart, Robert M G; Zhu, Julia; Park, Sohee; Woodman, Geoffrey F

2015-07-28

Executive control and flexible adjustment of behavior following errors are essential to adaptive functioning. Loss of adaptive control may be a biomarker of a wide range of neuropsychiatric disorders, particularly in the schizophrenia spectrum. Here, we provide support for the view that oscillatory activity in the frontal cortex underlies adaptive adjustments in cognitive processing following errors. Compared with healthy subjects, patients with schizophrenia exhibited low frequency oscillations with abnormal temporal structure and an absence of synchrony over medial-frontal and lateral-prefrontal cortex following errors. To demonstrate that these abnormal oscillations were the origin of the impaired adaptive control in patients with schizophrenia, we applied noninvasive dc electrical stimulation over the medial-frontal cortex. This noninvasive stimulation descrambled the phase of the low-frequency neural oscillations that synchronize activity across cortical regions. Following stimulation, the behavioral index of adaptive control was improved such that patients were indistinguishable from healthy control subjects. These results provide unique causal evidence for theories of executive control and cortical dysconnectivity in schizophrenia.

Evolution of the dynamic properties of the cortex-basal ganglia network after dopaminergic depletion in rats.

PubMed

Dejean, Cyril; Nadjar, Agnes; Le Moine, Catherine; Bioulac, Bernard; Gross, Christian E; Boraud, Thomas

2012-05-01

It is well established that parkinsonian syndrome is associated with alterations of neuronal activity temporal pattern basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in Parkinson's disease patients as well as animal models such as 6-hydroxydopamine treated rats. We recently demonstrated that this increase in oscillatory synchronization is present during high-voltage spindles (HVS) probably underpinned by the disorganization of cortex-BG interactions. Here we investigated the time course of both oscillatory and motor alterations. For that purpose we performed daily simultaneous recordings of neuronal activity in motor cortex, striatum and substantia nigra pars reticulata (SNr), before and after 6-hydroxydopamine lesion in awake rats. After a brief non-dopamine-specific desynchronization, oscillatory activity first increased during HVS followed by progressive motor impairment and the shortening of SNr activation delay. While the oscillatory firing increase reflects dopaminergic depletion, response alteration in SNr neurons is closely related to motor symptom. Copyright © 2012 Elsevier Inc. All rights reserved.

Prism adaptation improves ego-centered but not allocentric neglect in early rehabilitation patients.

PubMed

Gossmann, Anja; Kastrup, Andreas; Kerkhoff, Georg; López-Herrero, Carmen; Hildebrandt, Helmut

2013-01-01

Unilateral neglect due to parieto-temporo-frontal lesions has a negative impact on the success of rehabilitation, and prism adaptation (PA) enhances recovery from neglect. However, it is unclear if this effect holds also in severely impaired patients and/or in the postacute phase of rehabilitation. Moreover, it is not known whether PA affects all aspects of neglect recovery or ego-centered spatial orientation only. Sixteen patients in a postacute stage (on average 36 days after a large right cerebrovascular stroke) were entered into a series of single case design studies with 4 measurements: 2 before and 2 after 1 week of PA treatment. All patients had severe neglect (showing trunk, head, and eye deviation; canceling less than 20% of targets in a visual cancellation test). Lesions were transferred to a standard brain to analyze size and location. Patients improved in cued body orientation and in the cancellation task, that is, in ego-centered neglect. However, none of the measures used to evaluate neglect of left side of objects irrespective of their position on the right or left side of the patient (allocentric neglect) showed an improvement. Treatment effects were not influenced by total lesion size, but lesions including the postcentral cortex were related to smaller recovery gains. PA is helpful in treating severely impaired patients in the postacute phase, but the effect is restricted to ego-centered neglect. Lesions in the postcentral cortex (middle occipito-temporal, middle temporal, and posterior parietal areas) seem to limit the effect of PA.

A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats.

PubMed

Treviño, Samuel; Aguilar-Alonso, Patrícia; Flores Hernandez, Jose Angel; Brambila, Eduardo; Guevara, Jorge; Flores, Gonzalo; Lopez-Lopez, Gustavo; Muñoz-Arenas, Guadalupe; Morales-Medina, Julio Cesar; Toxqui, Veronica; Venegas, Berenice; Diaz, Alfonso

2015-09-01

A high calorie intake can induce the appearance of the metabolic syndrome (MS), which is a serious public health problem because it affects glucose levels and triglycerides in the blood. Recently, it has been suggested that MS can cause complications in the brain, since chronic hyperglycemia and insulin resistance are risk factors for triggering neuronal death by inducing a state of oxidative stress and inflammatory response that affect cognitive processes. This process, however, is not clear. In this study, we evaluated the effect of the consumption of a high-calorie diet (HCD) on both neurodegeneration and spatial memory impairment in rats. Our results demonstrated that HCD (90 day consumption) induces an alteration of the main energy metabolism markers, indicating the development of MS in rats. Moreover, an impairment of spatial memory was observed. Subsequently, the brains of these animals showed activation of an inflammatory response (increase in reactive astrocytes and interleukin1-β as well as tumor necrosis factor-α) and oxidative stress (reactive oxygen species and lipid peroxidation), causing a reduction in the number of neurons in the temporal cortex and hippocampus. Altogether, these results suggest that a HCD promotes the development of MS and contributes to the development of a neurodegenerative process and cognitive failure. In this regard, it is important to understand the relationship between MS and neuronal damage in order to prevent the onset of neurodegenerative disorders. © 2015 Wiley Periodicals, Inc.

IMPAIRED VERBAL COMPREHENSION OF QUANTIFIERS IN CORTICOBASAL SYNDROME

PubMed Central

Troiani, Vanessa; Clark, Robin; Grossman, Murray

2011-01-01

Objective Patients with Corticobasal Syndrome (CBS) have atrophy in posterior parietal cortex. This region of atrophy has been previously linked with their quantifier comprehension difficulty, but previous studies used visual stimuli, making it difficult to account for potential visuospatial deficits in CBS patients. The current study evaluated comprehension of generalized quantifiers using strictly verbal materials. Method CBS patients, a brain-damaged control group (consisting of Alzheimer's Disease and frontotemporal dementia), and age-matched controls participated in this study. We assessed familiar temporal, spatial, and monetary domains of verbal knowledge comparatively. Judgment accuracy was only evaluated in statements for which patients demonstrated accurate factual knowledge about the target domain. Results We found that patients with CBS are significantly impaired in their ability to evaluate quantifiers compared to healthy seniors and a brain-damaged control group, even in this strictly visual task. This impairment was seen in the vast majority of individual CBS patients. Conclusions These findings offer additional evidence of quantifier impairment in CBS patients and emphasize that this impairment cannot be attributed to potential spatial processing impairments in patients with parietal disease. PMID:21381823

A functional magnetic resonance imaging investigation of theory of mind impairments in patients with temporal lobe epilepsy.

PubMed

Hennion, Sophie; Delbeuck, Xavier; Koelkebeck, Katja; Brion, Marine; Tyvaert, Louise; Plomhause, Lucie; Derambure, Philippe; Lopes, Renaud; Szurhaj, William

2016-12-01

Although patients with mesial temporal lobe epilepsy (mTLE) are known to have theory of mind (ToM) impairments, the latter's neural functional bases have yet to be explored. We used functional magnetic resonance imaging (fMRI) to gain insights into the neural dysfunction associated with ToM impairments in patients with mTLE. Twenty-five patients (12 and 13 with right and left mTLE, respectively) and 25 healthy controls performed the "animated shapes" task during fMRI. This complex ToM task requires both explicit reasoning about mental states and implicit processing of information on biological motion and action. The animated shapes evoke both ToM and non-ToM interaction perception, and the corresponding neural activation patterns were compared. Behavioral performance (i.e. categorization of the interactions) was also recorded. Relative to healthy controls, both patients with right and left mTLE were impaired in categorizing ToM interactions. The fMRI results showed that both patients with right and left mTLE had less intense neural activation (relative to controls) in regions involved in the implicit component of ToM processes (i.e. the fusiform gyrus in patients with right mTLE and the supplementary motor area in patients with left mTLE). In patients with right mTLE, we also observed more intense activation (relative to controls) in regions involved in the explicit component of ToM processes (i.e. the dorsal medial prefrontal cortex); age at onset of epilepsy also mediated activation in regions involved in the explicit component (i.e. the ventral medial prefrontal cortex and the temporoparietal junction). Patients with left mTLE displayed greater activation of the contralateral mesial regions (relative to controls); we speculate that this may correspond to the deployment of a compensatory mechanism. This study provides insights into the disturbances of the implicit/explicit ToM neural network in patients with mTLE. These impairments in the ToM neural network depend on clinical characteristics, such as the laterality (right or left mTLE) and the age at onset of epilepsy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medial temporal lobe contributions to short-term memory for faces

PubMed Central

Race, Elizabeth; LaRocque, Karen F.; Keane, Margaret M.; Verfaellie, Mieke

2015-01-01

The role of the medial temporal lobes (MTL) in short-term memory (STM) remains a matter of debate. While imaging studies commonly show hippocampal activation during short-delay memory tasks, evidence from amnesic patients with MTL lesions is mixed. It has been argued that apparent STM impairments in amnesia may reflect long-term memory (LTM) contributions to performance. We challenge this conclusion by demonstrating that MTL amnesic patients show impaired delayed matching-to-sample (DMS) for faces in a task that meets both a traditional delay-based and a recently proposed distractor-based criterion for classification as a STM task. In Experiment 1, we demonstrate that our face DMS task meets the proposed distractor-based criterion for STM classification, in that extensive processing of delay-period distractor stimuli disrupts performance of healthy individuals. In Experiment 2, MTL amnesic patients with lesions extending into anterior subhippocampal cortex, but not patients with lesions limited to the hippocampus, show impaired performance on this task without distraction at delays as short as 8s, within temporal range of delay-based STM classification, in the context of intact perceptual matching performance. Experiment 3 provides support for the hypothesis that STM for faces relies on configural processing by showing that the extent to which healthy participants’ performance is disrupted by interference depends on the configural demands of the distractor task. Together, these findings are consistent with the notion that the amnesic impairment in STM for faces reflects a deficit in configural processing associated with subhippocampal cortices and provide novel evidence that the MTL supports cognition beyond the LTM domain. PMID:23937185

CORRELATION INDICES OF CEREBRAL HEMODYNAMICS AND ELECTRICAL ACTIVITY IN CHILDREN WITH IMPAIRED MOTOR SKILLS.

PubMed

Golovchenko, I V; Hayday, M I

The correlations between the indicators of cerebral hemodynamics and electrical activity in children with impaired motor skills of central origin (children with cerebral palsy) were investigated. There is established a high number of links between indicators of rheoencephalogram (REG) and electroencephalogram (EEG) in the left cerebral hemisphere than in the right. In frontomastoidal allocation 19 correlations and in occipitomastoidal - 59 links. We suppose that poor circulation in vertebroplasty-basilar system leads to the defeat of the brain stem, which, with afferent pathways of the reticular formation, connects the thalamus with the cortex. In the reticular formation there is an inhibition of ascending activators influences, which eland to decreasing of the cortex is tonus. You can talk about the functional immaturity of the system of nonspecific activation by the reticular formation of the brain stem. Children with violation of motor activity had significantly more negative and positive significant and high correlation among the existing indicators of electric brain activity and cerebral hemodynamics, in our opinion, is due to the development of interconnection compensation that is carried out by adjustment of the functional systems and the formation of new forms of adaptive responses in conditions of disontogenetik. Feature correlation pattern of the EEG, of children with disorders of motor activity, is associated with a significantly great number of high and significant correlations between measures of electrical brain activity in the δ- and q- rhythms, especially in the temporal areas of the cerebral cortex. According to visual analysis of EEG there is revealed a common manifestation of changes of bioelectric brain activity in children with disorders of motor activity. This is manifested in the development of paroxysmal activity of action potentials of θ- and δ-rhythms with the focus of activity in the anterior areas of the cerebral cortex; the formation of a mosaic representation of the θ-rhythms in temporal areas; the presence of hypersynchronous a-paroxysms in the posterior areas of the cerebral cortex. The given facts testify to activation of mechanisms of limbic-neocortical systems and synchronizing influences of the reticular formation of the stem and diencephalic structures. There is also detected greater number of correlations when occipitomastoidal registration was lone it reflects compensatory redistribution of cerebral blood flow over the affected structures of brain stem structures that are associated with the provision of cortical functions.

Tissue Expressions of Soluble Human Epoxide Hydrolase-2 Enzyme in Patients with Temporal Lobe Epilepsy.

PubMed

Ahmedov, Merdin Lyutviev; Kemerdere, Rahsan; Baran, Oguz; Inal, Berrin Bercik; Gumus, Alper; Coskun, Cihan; Yeni, Seher Naz; Eren, Bulent; Uzan, Mustafa; Tanriverdi, Taner

2017-10-01

We sought to simply demonstrate how levels of soluble human epoxide hydrolase-2 show changes in both temporal the cortex and hippocampal complex in patients with temporal lobe epilepsy. A total of 20 patients underwent anterior temporal lobe resection due to temporal lobe epilepsy. The control group comprised 15 people who died in traffic accidents or by falling from a height, and their autopsy findings were included. Adequately sized temporal cortex and hippocampal samples were removed from each patient during surgery, and the same anatomic structures were removed from the control subjects during the autopsy procedures. Each sample was stored at -80°C as rapidly as possible until the enzyme assay. The temporal cortex in the epilepsy patients had a significantly higher enzyme level than did the temporal cortex of the control group (P = 0.03). Correlation analysis showed that as the enzyme level increases in the temporal cortex, it also increases in the hippocampal complex (r 2  = 0.06, P = 0.00001). More important, enzyme tissue levels showed positive correlations with seizure frequency in both the temporal cortex and hippocampal complex in patients (r 2  = 0.7, P = 0.00001 and r 2  = 0.4, P = 0.003, respectively). The duration of epilepsy was also positively correlated with the hippocampal enzyme level (r 2  = 0.06, P = 0.00001). Soluble human epoxy hydrolase enzyme-2 is increased in both lateral and medial temporal tissues in temporal lobe epilepsy. Further studies should be conducted as inhibition of this enzyme has resulted in a significant decrease in or stopping of seizures and attenuated neuroinflammation in experimental epilepsy models in the current literature. Copyright © 2017 Elsevier Inc. All rights reserved.

Disturbed functional connectivity within the left prefrontal cortex and sensorimotor areas predicts impaired cognitive speed in patients with first-episode schizophrenia.

PubMed

Krukow, Paweł; Jonak, Kamil; Karakuła-Juchnowicz, Hanna; Podkowiński, Arkadiusz; Jonak, Katarzyna; Borys, Magdalena; Harciarek, Michał

2018-05-30

This study aimed at identifying abnormal cortico-cortical functional connectivity patterns that could predict cognitive slowing in patients with schizophrenia. A group of thirty-two patients with the first-episode schizophrenia and comparable healthy controls underwent resting-state qEEG and cognitive assessment. Phase Lag Index (PLI) was applied as a connectivity index and the synchronizations were analyzed in six frequencies. Pairs of electrodes were grouped to separately cover frontal, temporal, central, parietal and occipital regions. PLI was calculated for intra-regional connectivity and between-regions connectivity. Computer version processing speed tests were applied to control for possible fluctuations in cognitive efficiency during the performance of the tasks. In the group of patients, in comparison to healthy controls, significantly higher PLI values were recorded in theta frequency, especially in the posterior areas and decreased PLI in low-alpha frequency within the frontal regions. Mean PLI in gamma frequency was also lower in the patients group. Regression analysis showed that lower intra-regional PLI for left frontal cortex and higher PLI within somatosensory cortex in theta band, together with the duration of untreated psychosis, proved to be significant predictors of impaired processing speed in first-episode patients. Our investigation confirmed that disrupted cortico-cortical synchronization contributes to cognitive slowing in schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Prefrontal activity and impaired memory encoding strategies in schizophrenia.

PubMed

Guimond, Synthia; Hawco, Colin; Lepage, Martin

2017-08-01

Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome. Copyright © 2017. Published by Elsevier Ltd.

Network analysis of brain activations in working memory: behavior and age relationships.

PubMed

Mencl, W E; Pugh, K R; Shaywitz, S E; Shaywitz, B A; Fulbright, R K; Constable, R T; Skudlarski, P; Katz, L; Marchione, K E; Lacadie, C; Gore, J C

2000-10-01

Forty-six middle-aged female subjects were scanned using functional Magnetic Resonance Imaging (fMRI) during performance of three distinct stages of a working memory task-encoding, rehearsal, and recognition-for both printed pseudowords and visual forms. An expanse of areas, involving the inferior frontal, parietal, and extrastriate cortex, was active in response to stimuli during both the encoding and recognition periods. Additional increases during memory recognition were seen in right prefrontal regions, replicating a now-common finding [for reviews, see Fletcher et al. (1997) Trends Neurosci 20:213-218; MacLeod et al. (1998) NeuroImage 7:41-48], and broadly supporting the Hemispheric Encoding/Retrieval Asymmetry hypothesis [Tulving et al. (1994) Proc Natl Acad Sci USA 91:2016-2020]. Notably, this asymmetry was not qualified by the type of material being processed. A few sites demonstrated higher activity levels during the rehearsal period, in the absence of any new stimuli, including the medial extrastriate, precuneus, and the medial temporal lobe. Further analyses examined relationships among subjects' brain activations, age, and behavioral scores on working memory tests, acquired outside the scanner. Correlations between brain scores and behavior scores indicated that activations in a number of areas, mainly frontal, were associated with performance. A multivariate analysis, Partial Least Squares [McIntosh et al. (1996) NeuroImage 3:143-157, (1997) Hum Brain Map 5:323-327], was then used to extract component effects from this large set of univariate correlations. Results indicated that better memory performance outside the scanner was associated with higher activity at specific sites within the frontal and, additionally, the medial temporal lobes. Analysis of age effects revealed that younger subjects tended to activate more than older subjects in areas of extrastriate cortex, medial frontal cortex, and the right medial temporal lobe; older subjects tended to activate more than younger subjects in the insular cortex, right inferior temporal lobe, and right inferior frontal gyrus. These results extend recent reports indicating that these regions are specifically involved in the memory impairments seen with aging. Copyright 2000 Wiley-Liss, Inc.

Three-Dimensional Gray Matter Atrophy Mapping in Mild Cognitive Impairment and Mild Alzheimer Disease

PubMed Central

Apostolova, Liana G.; Steiner, Calen A.; Akopyan, Gohar G.; Dutton, Rebecca A.; Hayashi, Kiralee M.; Toga, Arthur W.; Cummings, Jeffrey L.; Thompson, Paul M.

2011-01-01

Background Alzheimer disease (AD) is the most common form of dementia worldwide. Mild cognitive impairment (MCI) is the recent terminology for patients with cognitive deficiencies in the absence of functional decline. Most patients with MCI harbor the pathologic changes of AD and demonstrate transition to dementia at a rate of 10% to 15% per year. Patients with AD and MCI experience progressive brain atrophy. Objective To analyze the structural magnetic resonance imaging data for 24 patients with amnestic MCI and 25 patients with mild AD using an advanced 3-dimensional cortical mapping technique. Design Cross-sectional cohort design. Patients/Methods We analyzed the structural magnetic resonance imaging data of 24 amnestic MCI (mean MMSE, 28.1; SD, 1.7) and 25 mild AD patients (all MMSE scores, >18; mean MMSE, 23.7; SD, 2.9) using an advanced 3-dimensional cortical mapping technique. Results We observed significantly greater cortical atrophy in patients with mild AD. The entorhinal cortex, right more than left lateral temporal cortex, right parietal cortex, and bilateral precuneus showed 15% more atrophy and the remainder of the cortex primarily exhibited 10% to 15% more atrophy in patients with mild AD than in patients with amnestic MCI. Conclusion There are striking cortical differences between mild AD and the immediately preceding cognitive state of amnestic MCI. Cortical areas affected earlier in the disease process are more severely affected than those that are affected late. Our method may prove to be a reliable in vivo disease-tracking technique that can also be used for evaluating disease-modifying therapies in the future. PMID:17923632

The frontal-anatomic specificity of design fluency repetitions and their diagnostic relevance for behavioral variant frontotemporal dementia.

PubMed

Possin, Katherine L; Chester, Serana K; Laluz, Victor; Bostrom, Alan; Rosen, Howard J; Miller, Bruce L; Kramer, Joel H

2012-09-01

On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).

Brain mitochondrial metabolic dysfunction and glutamate level reduction in the pilocarpine model of temporal lobe epilepsy in mice

PubMed Central

Smeland, Olav B; Hadera, Mussie G; McDonald, Tanya S; Sonnewald, Ursula; Borges, Karin

2013-01-01

Although certain metabolic characteristics such as interictal glucose hypometabolism are well established for temporal lobe epilepsy (TLE), its pathogenesis still remains unclear. Here, we performed a comprehensive study of brain metabolism in a mouse model of TLE, induced by pilocarpine–status epilepticus (SE). To investigate glucose metabolism, we injected mice 3.5–4 weeks after SE with [1,2-13C]glucose before microwave fixation of the head. Using 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography—mass spectrometry and high-pressure liquid chromatography, we quantified metabolites and 13C labeling in extracts of cortex and hippocampal formation (HF). Hippocampal levels of glutamate, glutathione and alanine were decreased in pilocarpine–SE mice compared with controls. Moreover, the contents of N-acetyl aspartate, succinate and reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H were decreased in HF indicating impairment of mitochondrial function. In addition, the reduction in 13C enrichment of hippocampal citrate and malate suggests decreased tricarboxylic acid (TCA) cycle turnover in this region. In cortex, we found reduced 13C labeling of glutamate, glutamine and aspartate via the pyruvate carboxylation and pyruvate dehydrogenation pathways, suggesting slower turnover of these amino acids and/or the TCA cycle. In conclusion, mitochondrial metabolic dysfunction and altered amino-acid metabolism is found in both cortex and HF in this epilepsy model. PMID:23611869

Semantics of the visual environment encoded in parahippocampal cortex

PubMed Central

Bonner, Michael F.; Price, Amy Rose; Peelle, Jonathan E.; Grossman, Murray

2016-01-01

Semantic representations capture the statistics of experience and store this information in memory. A fundamental component of this memory system is knowledge of the visual environment, including knowledge of objects and their associations. Visual semantic information underlies a range of behaviors, from perceptual categorization to cognitive processes such as language and reasoning. Here we examine the neuroanatomic system that encodes visual semantics. Across three experiments, we found converging evidence indicating that knowledge of verbally mediated visual concepts relies on information encoded in a region of the ventral-medial temporal lobe centered on parahippocampal cortex. In an fMRI study, this region was strongly engaged by the processing of concepts relying on visual knowledge but not by concepts relying on other sensory modalities. In a study of patients with the semantic variant of primary progressive aphasia (semantic dementia), atrophy that encompassed this region was associated with a specific impairment in verbally mediated visual semantic knowledge. Finally, in a structural study of healthy adults from the fMRI experiment, gray matter density in this region related to individual variability in the processing of visual concepts. The anatomic location of these findings aligns with recent work linking the ventral-medial temporal lobe with high-level visual representation, contextual associations, and reasoning through imagination. Together this work suggests a critical role for parahippocampal cortex in linking the visual environment with knowledge systems in the human brain. PMID:26679216

Semantics of the Visual Environment Encoded in Parahippocampal Cortex.

PubMed

Bonner, Michael F; Price, Amy Rose; Peelle, Jonathan E; Grossman, Murray

2016-03-01

Semantic representations capture the statistics of experience and store this information in memory. A fundamental component of this memory system is knowledge of the visual environment, including knowledge of objects and their associations. Visual semantic information underlies a range of behaviors, from perceptual categorization to cognitive processes such as language and reasoning. Here we examine the neuroanatomic system that encodes visual semantics. Across three experiments, we found converging evidence indicating that knowledge of verbally mediated visual concepts relies on information encoded in a region of the ventral-medial temporal lobe centered on parahippocampal cortex. In an fMRI study, this region was strongly engaged by the processing of concepts relying on visual knowledge but not by concepts relying on other sensory modalities. In a study of patients with the semantic variant of primary progressive aphasia (semantic dementia), atrophy that encompassed this region was associated with a specific impairment in verbally mediated visual semantic knowledge. Finally, in a structural study of healthy adults from the fMRI experiment, gray matter density in this region related to individual variability in the processing of visual concepts. The anatomic location of these findings aligns with recent work linking the ventral-medial temporal lobe with high-level visual representation, contextual associations, and reasoning through imagination. Together, this work suggests a critical role for parahippocampal cortex in linking the visual environment with knowledge systems in the human brain.

Diminution of context association memory structure in subjects with subjective cognitive decline.

PubMed

Fan, Ling-Yun; Lai, Ya-Mei; Chen, Ta-Fu; Hsu, Yung-Chin; Chen, Pin-Yu; Huang, Kuo-Zhou; Cheng, Ting-Wen; Tseng, Wen-Yi Isaac; Hua, Mau-Sun; Chen, Ya-Fang; Chiu, Ming-Jang

2018-06-01

Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale-III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content-related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage. © 2018 Wiley Periodicals, Inc.

Clinical symptoms and alpha band resting-state functional connectivity imaging in patients with schizophrenia: implications for novel approaches to treatment

PubMed Central

Hinkley, Leighton B.N.; Vinogradov, Sophia; Guggisberg, Adrian G.; Fisher, Melissa; Findlay, Anne M.; Nagarajan, Srikantan S.

2011-01-01

Background Schizophrenia is associated with functional decoupling between cortical regions, but we do not know whether and where this occurs in low-frequency electromagnetic oscillations. The goal of this study was to use magnetoencephalography (MEG) to identify brain regions that exhibit abnormal resting-state connectivity in the alpha frequency range in patients with schizophrenia and investigate associations between functional connectivity and clinical symptoms in stable outpatient participants. Method Thirty patients with schizophrenia and fifteen healthy comparison participants were scanned in resting-state MEG (eyes closed). Functional connectivity MEGI (fcMEGI) data were reconstructed globally in the alpha range, quantified by the mean imaginary coherence between a voxel and the rest of the brain. Results In patients, decreased connectivity was observed in left pre-frontal cortex (PFC) and right superior temporal cortex while increased connectivity was observed in left extrastriate cortex and the right inferior PFC. Functional connectivity of left inferior parietal cortex was negatively related to positive symptoms. Low left PFC connectivity was associated with negative symptoms. Functional connectivity of midline PFC was negatively correlated with depressed symptoms. Functional connectivity of right PFC was associated with other (cognitive) symptoms. Conclusions This study demonstrates direct functional disconnection in schizophrenia between specific cortical fields within low-frequency resting-state oscillations. Impaired alpha coupling in frontal, parietal, and temporal regions is associated with clinical symptoms in these stable outpatients. Our findings indicate that this level of functional disconnection between cortical regions is an important treatment target in schizophrenia. PMID:21861988

Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy.

PubMed

Campo, Pablo; Garrido, Marta I; Moran, Rosalyn J; García-Morales, Irene; Poch, Claudia; Toledano, Rafael; Gil-Nagel, Antonio; Dolan, Raymond J; Friston, Karl J

2013-05-15

Mesial temporal lobe epilepsy (mTLE) is the most prevalent form of focal epilepsy, and hippocampal sclerosis (HS) is considered the most frequent associated pathological finding. Recent connectivity studies have shown that abnormalities, either structural or functional, are not confined to the affected hippocampus, but can be found in other connected structures within the same hemisphere, or even in the contralesional hemisphere. Despite the role of hippocampus in memory functions, most of these studies have explored network properties at resting state, and in some cases compared connectivity values with neuropsychological memory scores. Here, we measured magnetoencephalographic responses during verbal working memory (WM) encoding in left mTLE patients and controls, and compared their effective connectivity within a frontotemporal network using dynamic causal modelling. Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal cortex (IFC), and the medial temporal lobe (MTL). Test for differences in effective connectivity revealed that patients exhibited decreased ipsilesional MTL-ITC backward connectivity, and increased bidirectional IFC-MTL connectivity in the contralesional hemisphere. Critically, a negative correlation was observed between these changes in patients, with decreases in ipsilesional coupling among temporal sources associated with increases contralesional frontotemporal interactions. Furthermore, contralesional frontotemporal interactions were inversely related to task performance and level of education. The results demonstrate that unilateral sclerosis induced local and remote changes in the dynamic organization of a distributed network supporting verbal WM. Crucially, pre-(peri) morbid factors (educational level) were reflected in both cognitive performance and (putative) compensatory changes in physiological coupling. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-Term Temporal Imprecision of Information Coding in the Anterior Cingulate Cortex of Mice with Peripheral Inflammation or Nerve Injury

PubMed Central

Li, Xiang-Yao; Wang, Ning; Wang, Yong-Jie; Zuo, Zhen-Xing; Koga, Kohei; Luo, Fei

2014-01-01

Temporal properties of spike firing in the central nervous system (CNS) are critical for neuronal coding and the precision of information storage. Chronic pain has been reported to affect cognitive and emotional functions, in addition to trigger long-term plasticity in sensory synapses and behavioral sensitization. Less is known about the possible changes in temporal precision of cortical neurons in chronic pain conditions. In the present study, we investigated the temporal precision of action potential firing in the anterior cingulate cortex (ACC) by using both in vivo and in vitro electrophysiological approaches. We found that peripheral inflammation caused by complete Freund's adjuvant (CFA) increased the standard deviation (SD) of spikes latency (also called jitter) of ∼51% of recorded neurons in the ACC of adult rats in vivo. Similar increases in jitter were found in ACC neurons using in vitro brain slices from adult mice with peripheral inflammation or nerve injury. Bath application of glutamate receptor antagonists CNQX and AP5 abolished the enhancement of jitter induced by CFA injection or nerve injury, suggesting that the increased jitter depends on the glutamatergic synaptic transmission. Activation of adenylyl cyclases (ACs) by bath application of forskolin increased jitter, whereas genetic deletion of AC1 abolished the change of jitter caused by CFA inflammation. Our study provides strong evidence for long-term changes of temporal precision of information coding in cortical neurons after peripheral injuries and explains neuronal mechanism for chronic pain caused cognitive and emotional impairment. PMID:25100600

Effects of gamma-aminobutyric acid-modulating drugs on working memory and brain function in patients with schizophrenia.

PubMed

Menzies, Lara; Ooi, Cinly; Kamath, Shri; Suckling, John; McKenna, Peter; Fletcher, Paul; Bullmore, Ed; Stephenson, Caroline

2007-02-01

Cognitive impairment causes morbidity in schizophrenia and could be due to abnormalities of cortical interneurons using the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). To test the predictions that cognitive and brain functional responses to GABA-modulating drugs are correlated and abnormal in schizophrenia. Pharmacological functional magnetic resonance imaging study of 2 groups, each undergoing scanning 3 times, using an N-back working memory task, after placebo, lorazepam, or flumazenil administration. Eleven patients with chronic schizophrenia were recruited from a rehabilitation service, and 11 healthy volunteers matched for age, sex, and premorbid IQ were recruited from the local community. Intervention Participants received 2 mg of oral lorazepam, a 0.9-mg intravenous flumazenil bolus followed by a flumazenil infusion of 0.0102 mg/min, or oral and intravenous placebo. Working memory performance was summarized by the target discrimination index at several levels of difficulty. Increasing (or decreasing) brain functional activation in response to increasing task difficulty was summarized by the positive (or negative) load response. Lorazepam impaired performance and flumazenil enhanced it; these cognitive effects were more salient in schizophrenic patients. Functional magnetic resonance imaging demonstrated positive load response in a frontoparietal system and negative load response in the temporal and posterior cingulate regions; activation of the frontoparietal cortex was positively correlated with deactivation of the temporocingulate cortex. After placebo administration, schizophrenic patients had abnormally attenuated activation of the frontoparietal cortex and deactivation of the temporocingulate cortex; this pattern was mimicked in healthy volunteers and exacerbated in schizophrenic patients by lorazepam. However, in schizophrenic patients, flumazenil enhanced deactivation of the temporocingulate and activation of the anterior cingulate cortices. The GABA-modulating drugs differentially affect working memory performance and brain function in schizophrenia. Cognitive impairment in schizophrenia may reflect abnormal inhibitory function and could be treated by drugs targeting GABA neurotransmission.

Variable disruption of a syntactic processing network in primary progressive aphasia.

PubMed

Wilson, Stephen M; DeMarco, Andrew T; Henry, Maya L; Gesierich, Benno; Babiak, Miranda; Miller, Bruce L; Gorno-Tempini, Maria Luisa

2016-11-01

Syntactic processing deficits are highly variable in individuals with primary progressive aphasia. Damage to left inferior frontal cortex has been associated with syntactic deficits in primary progressive aphasia in a number of structural and functional neuroimaging studies. However, a contrasting picture of a broader syntactic network has emerged from neuropsychological studies in other aphasic cohorts, and functional imaging studies in healthy controls. To reconcile these findings, we used functional magnetic resonance imaging to investigate the functional neuroanatomy of syntactic comprehension in 51 individuals with primary progressive aphasia, composed of all clinical variants and a range of degrees of syntactic processing impairment. We used trial-by-trial reaction time as a proxy for syntactic processing load, to determine which regions were modulated by syntactic processing in each patient, and how the set of regions recruited was related to whether syntactic processing was ultimately successful or unsuccessful. Relationships between functional abnormalities and patterns of cortical atrophy were also investigated. We found that the individual degree of syntactic comprehension impairment was predicted by left frontal atrophy, but also by functional disruption of a broader syntactic processing network, comprising left posterior frontal cortex, left posterior temporal cortex, and the left intraparietal sulcus and adjacent regions. These regions were modulated by syntactic processing in healthy controls and in patients with primary progressive aphasia with relatively spared syntax, but they were modulated to a lesser extent or not at all in primary progressive aphasia patients whose syntax was relatively impaired. Our findings suggest that syntactic comprehension deficits in primary progressive aphasia reflect not only structural and functional changes in left frontal cortex, but also disruption of a wider syntactic processing network. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Fornix and medial temporal lobe lesions lead to comparable deficits in complex visual perception.

PubMed

Lech, Robert K; Koch, Benno; Schwarz, Michael; Suchan, Boris

2016-05-04

Recent research dealing with the structures of the medial temporal lobe (MTL) has shifted away from exclusively investigating memory-related processes and has repeatedly incorporated the investigation of complex visual perception. Several studies have demonstrated that higher level visual tasks can recruit structures like the hippocampus and perirhinal cortex in order to successfully perform complex visual discriminations, leading to a perceptual-mnemonic or representational view of the medial temporal lobe. The current study employed a complex visual discrimination paradigm in two patients suffering from brain lesions with differing locations and origin. Both patients, one with extensive medial temporal lobe lesions (VG) and one with a small lesion of the anterior fornix (HJK), were impaired in complex discriminations while showing otherwise mostly intact cognitive functions. The current data confirmed previous results while also extending the perceptual-mnemonic theory of the MTL to the main output structure of the hippocampus, the fornix. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dyslexic children lack word selectivity gradients in occipito-temporal and inferior frontal cortex.

PubMed

Olulade, O A; Flowers, D L; Napoliello, E M; Eden, G F

2015-01-01

fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called "visual word form area", VWFA), is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007). Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009). Building on these studies, we here (1) investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2) compare typically reading with dyslexic children, and (3) examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We report absence of an IFC gradient and connectivity between the lateral aspect of the IFC and the anterior occipito-temporal cortex in the dyslexic children. Together, our results provide insights into the source of the anomalies reported in previous studies of dyslexia and add to the growing evidence of an orthographic role of IFC in reading.

The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis.

PubMed

Yang, Jie; Shu, Hua

2012-08-01

Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension. Copyright © 2012 Elsevier Inc. All rights reserved.

Opposite effects depending on learning and memory demands in dorsomedial prefrontal cortex lesioned rats performing an olfactory task.

PubMed

Chaillan, F A; Marchetti, E; Delfosse, F; Roman, F S; Soumireu-Mourat, B

1997-01-01

In this study, the functional properties of the dorsomedial prefrontal cortex (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue olfactory discrimination task, dmPFC lesioned animals improved performance across sessions more rapidly than operated control animals. In an olfactory task using fixed interval training, animals with similar lesions were impaired. Both effects, although opposite, can be explained by a temporal processing deficit. The present results seem to indicate that the dmPFC is required for timing, classified as part of non-declarative memory. As reference memory improved in the lesioned animals, the finding is that the dmPFC supports non-declarative memory and thus interacts with declarative memory in the long-term formation of the associations between a particular stimulus (olfactory cue) and particular responses.

Social anxiety disorder exhibit impaired networks involved in self and theory of mind processing.

PubMed

Cui, Qian; Vanman, Eric J; Long, Zhiliang; Pang, Yajing; Chen, Yuyan; Wang, Yifeng; Duan, Xujun; Chen, Heng; Gong, Qiyong; Zhang, Wei; Chen, Huafu

2017-08-01

Most previous studies regarding social anxiety disorder (SAD) have focused on the role of emotional dysfunction, while impairments in self- and theory of mind (ToM)-processing have relatively been neglected. This study utilised functional connectivity density (FCD), resting-state functional connectivity (RSFC) and discriminant analyses to investigate impairments in self- and ToM-related networks in patients with SAD. Patients with SAD exhibited decreased long-range FCD in the right rostral anterior cingulate cortex (rACC) and decreased short-range FCD in the right superior temporal gyrus (STG)-key nodes involved in self- and ToM-processing, respectively. Decreased RSFC of the right rACC and STG with widespread frontal, temporal, posteromedial, sensorimotor, and somatosensory, regions was also observed in patients with SAD. Altered RSFC between the right rACC and bilateral superior frontal gyrus, between the right rACC and right middle frontal gyrus, and within the right STG itself provided the greatest contribution to individual diagnoses of SAD, with an accuracy of 84.5%. These results suggest that a lack of cognitive inhibition on emotional self-referential processing as well as impairments in social information integration may play critical roles in the pathomechanism of SAD and highlight the importance of recognising such features in the diagnosis and treatment of SAD. © The Author (2017). Published by Oxford University Press.

Obsessive Compulsive Disorder Networks: Positron Emission Tomography and Neuropsychology Provide New Insights

PubMed Central

Millet, Bruno; Dondaine, Thibaut; Reymann, Jean-Michel; Bourguignon, Aurélie; Naudet, Florian; Jaafari, Nematollah; Drapier, Dominique; Turmel, Valérie; Mesbah, Habiba; Vérin, Marc; Le Jeune, Florence

2013-01-01

Background Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. Methods and Findings This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state 18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. Conclusion As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes. PMID:23326403

Touch activates human auditory cortex.

PubMed

Schürmann, Martin; Caetano, Gina; Hlushchuk, Yevhen; Jousmäki, Veikko; Hari, Riitta

2006-05-01

Vibrotactile stimuli can facilitate hearing, both in hearing-impaired and in normally hearing people. Accordingly, the sounds of hands exploring a surface contribute to the explorer's haptic percepts. As a possible brain basis of such phenomena, functional brain imaging has identified activations specific to audiotactile interaction in secondary somatosensory cortex, auditory belt area, and posterior parietal cortex, depending on the quality and relative salience of the stimuli. We studied 13 subjects with non-invasive functional magnetic resonance imaging (fMRI) to search for auditory brain areas that would be activated by touch. Vibration bursts of 200 Hz were delivered to the subjects' fingers and palm and tactile pressure pulses to their fingertips. Noise bursts served to identify auditory cortex. Vibrotactile-auditory co-activation, addressed with minimal smoothing to obtain a conservative estimate, was found in an 85-mm3 region in the posterior auditory belt area. This co-activation could be related to facilitated hearing at the behavioral level, reflecting the analysis of sound-like temporal patterns in vibration. However, even tactile pulses (without any vibration) activated parts of the posterior auditory belt area, which therefore might subserve processing of audiotactile events that arise during dynamic contact between hands and environment.

Resting metabolic connectivity in prodromal Alzheimer's disease. A European Alzheimer Disease Consortium (EADC) project.

PubMed

Morbelli, Silvia; Drzezga, Alex; Perneczky, Robert; Frisoni, Giovanni B; Caroli, Anna; van Berckel, Bart N M; Ossenkoppele, Rik; Guedj, Eric; Didic, Mira; Brugnolo, Andrea; Sambuceti, Gianmario; Pagani, Marco; Salmon, Eric; Nobili, Flavio

2012-11-01

We explored resting-state metabolic connectivity in prodromal Alzheimer's disease (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose-positron emission tomography of 36 patients with amnestic mild cognitive impairment who converted to Alzheimer's disease (AD) dementia after an average time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism in pAD showed less metabolic connectivity in patients than in CTR (autocorrelation and correlation with large temporal and frontal areas, respectively). pAD patients showed limited correlation even in selected nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal cortex (DLFC). On the contrary, in CTR group correlation was highlighted between hippocampi and precuneus/posterior cingulate and frontal cortex, and between dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The reduced metabolic connections both in hypometabolic and nonhypometabolic areas in pAD patients suggest that metabolic disconnection (reflecting early diaschisis) may antedate remote hypometabolism (early sign of synaptic degeneration). Copyright © 2012 Elsevier Inc. All rights reserved.

Spatial and temporal episodic memory retrieval recruit dissociable functional networks in the human brain.

PubMed

Ekstrom, Arne D; Bookheimer, Susan Y

2007-10-01

Imaging, electrophysiological studies, and lesion work have shown that the medial temporal lobe (MTL) is important for episodic memory; however, it is unclear whether different MTL regions support the spatial, temporal, and item elements of episodic memory. In this study we used fMRI to examine retrieval performance emphasizing different aspects of episodic memory in the context of a spatial navigation paradigm. Subjects played a taxi-driver game ("yellowcab"), in which they freely searched for passengers and delivered them to specific landmark stores. Subjects then underwent fMRI scanning as they retrieved landmarks, spatial, and temporal associations from their navigational experience in three separate runs. Consistent with previous findings on item memory, perirhinal cortex activated most strongly during landmark retrieval compared with spatial or temporal source information retrieval. Both hippocampus and parahippocampal cortex activated significantly during retrieval of landmarks, spatial associations, and temporal order. We found, however, a significant dissociation between hippocampal and parahippocampal cortex activations, with spatial retrieval leading to greater parahippocampal activation compared with hippocampus and temporal order retrieval leading to greater hippocampal activation compared with parahippocampal cortex. Our results, coupled with previous findings, demonstrate that the hippocampus and parahippocampal cortex are preferentially recruited during temporal order and spatial association retrieval--key components of episodic "source" memory.

Decoding Face Information in Time, Frequency and Space from Direct Intracranial Recordings of the Human Brain

PubMed Central

Oya, Hiroyuki; Howard, Matthew A.; Adolphs, Ralph

2008-01-01

Faces are processed by a neural system with distributed anatomical components, but the roles of these components remain unclear. A dominant theory of face perception postulates independent representations of invariant aspects of faces (e.g., identity) in ventral temporal cortex including the fusiform gyrus, and changeable aspects of faces (e.g., emotion) in lateral temporal cortex including the superior temporal sulcus. Here we recorded neuronal activity directly from the cortical surface in 9 neurosurgical subjects undergoing epilepsy monitoring while they viewed static and dynamic facial expressions. Applying novel decoding analyses to the power spectrogram of electrocorticograms (ECoG) from over 100 contacts in ventral and lateral temporal cortex, we found better representation of both invariant and changeable aspects of faces in ventral than lateral temporal cortex. Critical information for discriminating faces from geometric patterns was carried by power modulations between 50 to 150 Hz. For both static and dynamic face stimuli, we obtained a higher decoding performance in ventral than lateral temporal cortex. For discriminating fearful from happy expressions, critical information was carried by power modulation between 60–150 Hz and below 30 Hz, and again better decoded in ventral than lateral temporal cortex. Task-relevant attention improved decoding accuracy more than10% across a wide frequency range in ventral but not at all in lateral temporal cortex. Spatial searchlight decoding showed that decoding performance was highest around the middle fusiform gyrus. Finally, we found that the right hemisphere, in general, showed superior decoding to the left hemisphere. Taken together, our results challenge the dominant model for independent face representation of invariant and changeable aspects: information about both face attributes was better decoded from a single region in the middle fusiform gyrus. PMID:19065268

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

PubMed

Mohedano-Moriano, Alicia; Muñoz-López, Mónica; Sanz-Arigita, Ernesto; Pró-Sistiaga, Palma; Martínez-Marcos, Alino; Legidos-Garcia, María Ester; Insausti, Ana María; Cebada-Sánchez, Sandra; Arroyo-Jiménez, María Del Mar; Marcos, Pilar; Artacho-Pérula, Emilio; Insausti, Ricardo

2015-12-01

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown. © 2015 Wiley Periodicals, Inc.

A functional magnetic resonance imaging study mapping the episodic memory encoding network in temporal lobe epilepsy

PubMed Central

Sidhu, Meneka K.; Stretton, Jason; Winston, Gavin P.; Bonelli, Silvia; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Koepp, Matthias J.

2013-01-01

Functional magnetic resonance imaging has demonstrated reorganization of memory encoding networks within the temporal lobe in temporal lobe epilepsy, but little is known of the extra-temporal networks in these patients. We investigated the temporal and extra-temporal reorganization of memory encoding networks in refractory temporal lobe epilepsy and the neural correlates of successful subsequent memory formation. We studied 44 patients with unilateral temporal lobe epilepsy and hippocampal sclerosis (24 left) and 26 healthy control subjects. All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words with subsequent out-of-scanner recognition assessments. A blocked analysis was used to investigate activations during encoding and neural correlates of subsequent memory were investigated using an event-related analysis. Event-related activations were then correlated with out-of-scanner verbal and visual memory scores. During word encoding, control subjects activated the left prefrontal cortex and left hippocampus whereas patients with left hippocampal sclerosis showed significant additional right temporal and extra-temporal activations. Control subjects displayed subsequent verbal memory effects within left parahippocampal gyrus, left orbitofrontal cortex and fusiform gyrus whereas patients with left hippocampal sclerosis activated only right posterior hippocampus, parahippocampus and fusiform gyrus. Correlational analysis showed that patients with left hippocampal sclerosis with better verbal memory additionally activated left orbitofrontal cortex, anterior cingulate cortex and left posterior hippocampus. During face encoding, control subjects showed right lateralized prefrontal cortex and bilateral hippocampal activations. Patients with right hippocampal sclerosis showed increased temporal activations within the superior temporal gyri bilaterally and no increased extra-temporal areas of activation compared with control subjects. Control subjects showed subsequent visual memory effects within right amygdala, hippocampus, fusiform gyrus and orbitofrontal cortex. Patients with right hippocampal sclerosis showed subsequent visual memory effects within right posterior hippocampus, parahippocampal and fusiform gyri, and predominantly left hemisphere extra-temporal activations within the insula and orbitofrontal cortex. Correlational analysis showed that patients with right hippocampal sclerosis with better visual memory activated the amygdala bilaterally, right anterior parahippocampal gyrus and left insula. Right sided extra-temporal areas of reorganization observed in patients with left hippocampal sclerosis during word encoding and bilateral lateral temporal reorganization in patients with right hippocampal sclerosis during face encoding were not associated with subsequent memory formation. Reorganization within the medial temporal lobe, however, is an efficient process. The orbitofrontal cortex is critical to subsequent memory formation in control subjects and patients. Activations within anterior cingulum and insula correlated with better verbal and visual subsequent memory in patients with left and right hippocampal sclerosis, respectively, representing effective extra-temporal recruitment. PMID:23674488

Different forms of effective connectivity in primate frontotemporal pathways.

PubMed

Petkov, Christopher I; Kikuchi, Yukiko; Milne, Alice E; Mishkin, Mortimer; Rauschecker, Josef P; Logothetis, Nikos K

2015-01-23

It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex.

Different forms of effective connectivity in primate frontotemporal pathways

PubMed Central

Petkov, Christopher I.; Kikuchi, Yukiko; Milne, Alice E.; Mishkin, Mortimer; Rauschecker, Josef P.; Logothetis, Nikos K.

2015-01-01

It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex. PMID:25613079

Orbito-Frontal Cortex Is Necessary for Temporal Context Memory

ERIC Educational Resources Information Center

Duarte, Audrey; Henson, Richard N.; Knight, Robert T.; Emery, Tina; Graham, Kim S.

2010-01-01

Lesion and neuroimaging studies suggest that orbito-frontal cortex (OFC) supports temporal aspects of episodic memory. However, it is unclear whether OFC contributes to the encoding and/or retrieval of temporal context and whether it is selective for temporal relative to nontemporal (spatial) context memory. We addressed this issue with two…

Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function.

PubMed

Butts, Kelly A; Weinberg, Joanne; Young, Allan H; Phillips, Anthony G

2011-11-08

Enhanced dopamine efflux in the prefrontal cortex is a well-documented response to acute stress. However, the underlying mechanism(s) for this response is unknown. Using in vivo microdialysis, we demonstrate that blocking glucocorticoid receptors locally within the rat prefrontal cortex results in a reduction in stress-evoked dopamine efflux. In contrast, blocking glucocorticoid receptors in the ventral tegmental area did not affect stress-evoked dopamine efflux in the prefrontal cortex. Additionally, local administration of corticosterone into the prefrontal cortex increased prefrontal dopamine efflux. The functional impact of enhanced dopamine efflux evoked by acute stress was demonstrated using a cognitive task dependent on the prefrontal cortex and sensitive to impairment in working memory. Notably, stress-induced impairments in cognition were attenuated by blockade of glucocorticoid receptors in the prefrontal cortex. Taken together, these data demonstrate that glucocorticoids act locally within the prefrontal cortex to modulate mesocortical dopamine efflux leading to the cognitive impairments observed during acute stress.

Face-specific impairment in holistic perception following focal lesion of the right anterior temporal lobe.

PubMed

Busigny, Thomas; Van Belle, Goedele; Jemel, Boutheina; Hosein, Anthony; Joubert, Sven; Rossion, Bruno

2014-04-01

Recent studies have provided solid evidence for pure cases of prosopagnosia following brain damage. The patients reported so far have posterior lesions encompassing either or both the right inferior occipital cortex and fusiform gyrus, and exhibit a critical impairment in generating a sufficiently detailed holistic percept to individualize faces. Here, we extended these observations to include the prosopagnosic patient LR (Bukach, Bub, Gauthier, & Tarr, 2006), whose damage is restricted to the anterior region of the right temporal lobe. First, we report that LR is able to discriminate parametrically defined individual exemplars of nonface object categories as accurately and quickly as typical observers, which suggests that the visual similarity account of prosopagnosia does not explain his impairments. Then, we show that LR does not present with the typical face inversion effect, whole-part advantage, or composite face effect and, therefore, has impaired holistic perception of individual faces. Moreover, the patient is more impaired at matching faces when the facial part he fixates is masked than when it is selectively revealed by means of gaze contingency. Altogether these observations support the view that the nature of the critical face impairment does not differ qualitatively across patients with acquired prosopagnosia, regardless of the localization of brain damage: all these patients appear to be impaired to some extent at what constitutes the heart of our visual expertise with faces, namely holistic perception at a sufficiently fine-grained level of resolution to discriminate exemplars of the face class efficiently. This conclusion raises issues regarding the existing criteria for diagnosis/classification of patients as cases of apperceptive or associative prosopagnosia. Copyright © 2014 Elsevier Ltd. All rights reserved.

A dataset of multiresolution functional brain parcellations in an elderly population with no or mild cognitive impairment.

PubMed

Tam, Angela; Dansereau, Christian; Badhwar, AmanPreet; Orban, Pierre; Belleville, Sylvie; Chertkow, Howard; Dagher, Alain; Hanganu, Alexandru; Monchi, Oury; Rosa-Neto, Pedro; Shmuel, Amir; Breitner, John; Bellec, Pierre

2016-12-01

We present group eight resolutions of brain parcellations for clusters generated from resting-state functional magnetic resonance images for 99 cognitively normal elderly persons and 129 patients with mild cognitive impairment, pooled from four independent datasets. This dataset was generated as part of the following study: Common Effects of Amnestic Mild Cognitive Impairment on Resting-State Connectivity Across Four Independent Studies (Tam et al., 2015) [1]. The brain parcellations have been registered to both symmetric and asymmetric MNI brain templates and generated using a method called bootstrap analysis of stable clusters (BASC) (Bellec et al., 2010) [2]. We present two variants of these parcellations. One variant contains bihemisphereic parcels (4, 6, 12, 22, 33, 65, 111, and 208 total parcels across eight resolutions). The second variant contains spatially connected regions of interest (ROIs) that span only one hemisphere (10, 17, 30, 51, 77, 199, and 322 total ROIs across eight resolutions). We also present maps illustrating functional connectivity differences between patients and controls for four regions of interest (striatum, dorsal prefrontal cortex, middle temporal lobe, and medial frontal cortex). The brain parcels and associated statistical maps have been publicly released as 3D volumes, available in .mnc and .nii file formats on figshare and on Neurovault. Finally, the code used to generate this dataset is available on Github.

Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients

PubMed Central

Hojjat, Seyed-Parsa; Cantrell, Charles Grady; Vitorino, Rita; Feinstein, Anthony; Shirzadi, Zahra; MacIntosh, Bradley J.; Crane, David E.; Zhang, Lying; Morrow, Sarah A; Lee, Liesly; O’Connor, Paul; Carroll, Timothy J.; Aviv, Richard I.

2015-01-01

Purpose Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural MRI measures of cortical integrity are limited, although functional techniques such as pseudocontinuous Arterial Spin Labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the MACFIMS battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences. PMID:26754799

Functional neuroimaging of extraversion-introversion.

PubMed

Lei, Xu; Yang, Tianliang; Wu, Taoyu

2015-12-01

Neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography have provided an unprecedented neurobiological perspective for research on personality traits. Evidence from task-related neuroimaging has shown that extraversion is associated with activations in regions of the anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and the amygdala. Currently, resting-state neuroimaging is being widely used in cognitive neuroscience. Initial exploration of extraversion has revealed correlations with the medial prefrontal cortex, anterior cingulate cortex, insular cortex, and the precuneus. Recent research work has indicated that the long-range temporal dependence of the resting-state spontaneous oscillation has high test-retest reliability. Moreover, the long-range temporal dependence of the resting-state networks is highly correlated with personality traits, and this can be used for the prediction of extraversion. As the long-range temporal dependence reflects real-time information updating in individuals, this method may provide a new approach to research on personality traits.

Distinct neuronal coding schemes in memory revealed by selective erasure of fast synchronous synaptic transmission.

PubMed

Xu, Wei; Morishita, Wade; Buckmaster, Paul S; Pang, Zhiping P; Malenka, Robert C; Südhof, Thomas C

2012-03-08

Neurons encode information by firing spikes in isolation or bursts and propagate information by spike-triggered neurotransmitter release that initiates synaptic transmission. Isolated spikes trigger neurotransmitter release unreliably but with high temporal precision. In contrast, bursts of spikes trigger neurotransmission reliably (i.e., boost transmission fidelity), but the resulting synaptic responses are temporally imprecise. However, the relative physiological importance of different spike-firing modes remains unclear. Here, we show that knockdown of synaptotagmin-1, the major Ca(2+) sensor for neurotransmitter release, abrogated neurotransmission evoked by isolated spikes but only delayed, without abolishing, neurotransmission evoked by bursts of spikes. Nevertheless, knockdown of synaptotagmin-1 in the hippocampal CA1 region did not impede acquisition of recent contextual fear memories, although it did impair the precision of such memories. In contrast, knockdown of synaptotagmin-1 in the prefrontal cortex impaired all remote fear memories. These results indicate that different brain circuits and types of memory employ distinct spike-coding schemes to encode and transmit information. Copyright © 2012 Elsevier Inc. All rights reserved.

The contribution of LM to the neuroscience of movement vision

PubMed Central

Zihl, Josef; Heywood, Charles A.

2015-01-01

The significance of early and sporadic reports in the 19th century of impairments of motion vision following brain damage was largely unrecognized. In the absence of satisfactory post-mortem evidence, impairments were interpreted as the consequence of a more general disturbance resulting from brain damage, the location and extent of which was unknown. Moreover, evidence that movement constituted a special visual perception and may be selectively spared was similarly dismissed. Such skepticism derived from a reluctance to acknowledge that the neural substrates of visual perception may not be confined to primary visual cortex. This view did not persist. First, it was realized that visual movement perception does not depend simply on the analysis of spatial displacements and temporal intervals, but represents a specific visual movement sensation. Second persuasive evidence for functional specialization in extrastriate cortex, and notably the discovery of cortical area V5/MT, suggested a separate region specialized for motion processing. Shortly thereafter the remarkable case of patient LM was published, providing compelling evidence for a selective and specific loss of movement vision. The case is reviewed here, along with an assessment of its contribution to visual neuroscience. PMID:25741251

Abnormal object recall and anterior cingulate overactivation correlate with formal thought disorder in schizophrenia.

PubMed

Assaf, Michal; Rivkin, Paul R; Kuzu, Cheedem H; Calhoun, Vince D; Kraut, Michael A; Groth, Karyn M; Yassa, Michael A; Hart, John; Pearlson, Godfrey D

2006-03-01

The neural basis of formal thought disorder (FTD) is unknown. An influential theory is that FTD results from impaired semantic memory processing. We explored the neural correlates of semantic memory retrieval in schizophrenia using an imaging task assessing semantic object recall. Sixteen healthy control subjects and sixteen schizophrenia patients whose FTD symptoms were measured with the Thought Disorder Index completed a verbal object-recall task during functional magnetic resonance imaging. Participants viewed two words describing object features that either evoked (object recall) or did not evoke a semantic concept. Schizophrenia patients tended to overrecall objects for feature pairs that did not describe the same object. Functionally, rostral anterior cingulate cortex (ACC) activation in patients positively correlated with FTD severity during both correct recalled and overrecalled trials. Compared with control subjects, during object recalling, patients overactivated bilateral ACC, temporooccipital junctions, temporal poles and parahippocampi, right inferior frontal gyrus, and dorsolateral prefrontal cortex, but underactivated inferior parietal lobules. Our results support impaired semantic memory retrieval as underlying FTD pathophysiology. Schizophrenia patients showed abnormal activations of brain areas involved in semantic memory, verbal working memory, and initiation and suppression of conflicting responses, which were associated with semantic overrecall and FTD.

Medial temporal lobe contributions to short-term memory for faces.

PubMed

Race, Elizabeth; LaRocque, Karen F; Keane, Margaret M; Verfaellie, Mieke

2013-11-01

The role of the medial temporal lobes (MTL) in short-term memory (STM) remains a matter of debate. Whereas imaging studies commonly show hippocampal activation during short-delay memory tasks, evidence from amnesic patients with MTL lesions is mixed. It has been argued that apparent STM impairments in amnesia may reflect long-term memory (LTM) contributions to performance. We challenge this conclusion by demonstrating that MTL amnesic patients show impaired delayed matching-to-sample (DMS) for faces in a task that meets both a traditional delay-based and a recently proposed distractor-based criterion for classification as an STM task. In Experiment 1, we demonstrate that our face DMS task meets the proposed distractor-based criterion for STM classification, in that extensive processing of delay-period distractor stimuli disrupts performance of healthy individuals. In Experiment 2, MTL amnesic patients with lesions extending into anterior subhippocampal cortex, but not patients with lesions limited to the hippocampus, show impaired performance on this task without distraction at delays as short as 8 s, within temporal range of delay-based STM classification, in the context of intact perceptual matching performance. Experiment 3 provides support for the hypothesis that STM for faces relies on configural processing by showing that the extent to which healthy participants' performance is disrupted by interference depends on the configural demands of the distractor task. Together, these findings are consistent with the notion that the amnesic impairment in STM for faces reflects a deficit in configural processing associated with subhippocampal cortices and provide novel evidence that the MTL supports cognition beyond the LTM domain. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

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

Takaya, Shigetoshi; Kuperberg, Gina R.; Tufts Univ., Medford, MA

The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that themore » left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. As a result, the unique feature of the left AF is discussed in the context of the human capacity for language.« less

Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

DOE PAGES

Takaya, Shigetoshi; Kuperberg, Gina R.; Tufts Univ., Medford, MA; ...

2015-09-15

The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that themore » left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. As a result, the unique feature of the left AF is discussed in the context of the human capacity for language.« less

[Role of the orbitofrontal cortex in moral judgment].

PubMed

Mimura, Masaru

2010-11-01

The neural substrates of moral judgments have recently been advocated to consist of widely distributed brain networks including the orbitofrontal cortex (OFC), anterior temporal lobe and superior temporal gyrus. Moral judgments could be regarded as a conflict between the top-down rational/logical processes and the bottom-up irrational/emotional processes. Individuals with OFC damage are usually difficult to inhibit emotionally-driven outrages, thereby demonstrating severe impairment of moral judgments despite their well-preserved moral knowledge. Individuals with OFC damage frequently present with anti-social less moral behaviors. However, clinical observation indicates that some OFC patients may show "hypermoral" tendency in the sense that they are too strict to overlook other person's offense. Two representative cases with OFC damage were reported, both presented with extreme rage against others' offensive behaviors. To further elucidate the "hypermorality" of OFC patients, an experiment was performed in which patients with OFC damage and healthy control participants were asked to determine punishments for other's fictitious crimes that varied in perpetrator responsibility and crime severity. Individuals with OFC damage punished more strictly than healthy controls those persons for mitigating circumstances. The results are consistent with clinical observation of OFC patients' highly rigid and inflexible behaviors against third person's offense.

Efficient visual object and word recognition relies on high spatial frequency coding in the left posterior fusiform gyrus: evidence from a case-series of patients with ventral occipito-temporal cortex damage.

PubMed

Roberts, Daniel J; Woollams, Anna M; Kim, Esther; Beeson, Pelagie M; Rapcsak, Steven Z; Lambon Ralph, Matthew A

2013-11-01

Recent visual neuroscience investigations suggest that ventral occipito-temporal cortex is retinotopically organized, with high acuity foveal input projecting primarily to the posterior fusiform gyrus (pFG), making this region crucial for coding high spatial frequency information. Because high spatial frequencies are critical for fine-grained visual discrimination, we hypothesized that damage to the left pFG should have an adverse effect not only on efficient reading, as observed in pure alexia, but also on the processing of complex non-orthographic visual stimuli. Consistent with this hypothesis, we obtained evidence that a large case series (n = 20) of patients with lesions centered on left pFG: 1) Exhibited reduced sensitivity to high spatial frequencies; 2) demonstrated prolonged response latencies both in reading (pure alexia) and object naming; and 3) were especially sensitive to visual complexity and similarity when discriminating between novel visual patterns. These results suggest that the patients' dual reading and non-orthographic recognition impairments have a common underlying mechanism and reflect the loss of high spatial frequency visual information normally coded in the left pFG.

Screening for confabulations with the confabulation screen.

PubMed

Dalla Barba, Gianfranco; Brazzarola, Marta; Marangoni, Sara; La Corte, Valentina

2018-04-24

The objective of this work is to devise and validate a sensitive and specific test for confabulatory impairment. We conceived a screening test for confabulation, the Confabulation Screen (CS), a brief test using 10 questions of episodic memory (EM), where confabulators most frequently confabulate. It was postulated that the CS would predict confabulations not only in EM, but also in the other subordinate structures of personal temporality, namely the present and the future. Thirty confabulating amnesic patients of various aetiologies and 97 normal controls entered the study. Participants were administered the CS and the Confabulation Battery (Dalla Barba, G., & Decaix, C. (2009). "Do you remeber what you did on March 13 1985?" A case study of confabulatory hypermnesia. Cortex, 45(5), 566-574). Confabulations in the CS positively and significantly correlated with confabulations in personal temporality domains of the CB, namely EM, orientation in time and place and episodic plans. Conversely, as expected, they did not correlate with confabulations in impersonal temporality domains of the CB. Consistent with results of previous studies, the most frequently observed type of confabulation in the CS was Habits Confabulation. The CS had high construct validity and good discriminative validity in terms of sensitivity and specificity. Cut-off scores for clinical and research purposes are proposed. The CS provides efficient and valid screening for confabulatory impairment.

Altered cerebral activity associated with topiramate and its withdrawal in patients with epilepsy with language impairment: An fMRI study using the verb generation task.

PubMed

Tang, Yingying; Xia, Wei; Yu, Xiaofeng; Zhou, Bo; Wu, Xintong; Lui, Su; Luo, Chunyan; Huang, Xiaoqi; Ouyang, Luo; Chen, Qin; Gong, Qiyong; Zhou, Dong

2016-06-01

Topiramate (TPM) is well recognized for its negative effects on language in healthy volunteers and patients with epilepsy. The aim of this study was to investigate the brain activation and deactivation patterns in TPM-treated patients with epilepsy with language impairment and their dynamic alteration during TPM withdrawal using functional magnetic resonance imaging (fMRI) with the verb generation task (VGT). Twelve patients with epilepsy experiencing subjective language disfluency after TPM add-on treatment (TPM-on) and thirty sex- and age-matched healthy controls (HCs) were recruited. All subjects received a battery of neuropsychological tests and an fMRI scan with the VGT. Withdrawal of TPM was attempted in all patients. Only six patients reached complete withdrawal without seizure relapses (TPM-off), and these patients underwent a reassessment of neuropsychological and neuroimaging tests. The neuropsychological tests demonstrated objective language impairments in TPM-on patients. Compared with the HCs, the bilateral medial prefrontal cortex and the posterior midline and lateral parts of the default mode network (DMN) (including the bilateral posterior cingulate cortex (PCC), the right medial prefrontal cortex, the right angular gyrus, the right inferior temporal gyrus, and the bilateral supramarginal gyrus) in TPM-on patients failed to deactivate during the VGT. Their task-induced activation patterns were largely similar to those of the HCs. After TPM withdrawal, partial improvement of both task-induced deactivation of the DMN (the left parahippocampal gyrus and the bilateral PCC) and task-related activation of the language network (the right middle frontal gyrus and the left superior occipital gyrus) was identified along with partial improvement of neuropsychological tests. Task-induced deactivation is a more sensitive neuroimaging biomarker for the impaired language performance in patients administered TPM than task-induced activation. Disruption and reorganization of the balance between the DMN and the cortical language networks are found along with reversible TPM-related language impairment. These results may suggest an underlying brain mechanism by which TPM affects cognitive function. Copyright © 2016 Elsevier Inc. All rights reserved.

A real-world size organization of object responses in occipito-temporal cortex

PubMed Central

Konkle, Talia; Oliva, Aude

2012-01-01

SUMMARY While there are selective regions of occipito-temporal cortex that respond to faces, letters, and bodies, the large-scale neural organization of most object categories remains unknown. Here we find that object representations can be differentiated along the ventral temporal cortex by their real-world size. In a functional neuroimaging experiment, observers were shown pictures of big and small real-world objects (e.g. table, bathtub; paperclip, cup), presented at the same retinal size. We observed a consistent medial-to-lateral organization of big and small object preferences in the ventral temporal cortex, mirrored along the lateral surface. Regions in the lateral-occipital, infero-temporal, and parahippocampal cortices showed strong peaks of differential real-world size selectivity, and maintained these preferences over changes in retinal size and in mental imagery. These data demonstrate that the real-world size of objects can provide insight into the spatial topography of object representation. PMID:22726840

Impaired temporal, not just spatial, resolution in amblyopia.

PubMed

Spang, Karoline; Fahle, Manfred

2009-11-01

In amblyopia, neuronal deficits deteriorate spatial vision including visual acuity, possibly because of a lack of use-dependent fine-tuning of afferents to the visual cortex during infancy; but temporal processing may deteriorate as well. Temporal, rather than spatial, resolution was investigated in patients with amblyopia by means of a task based on time-defined figure-ground segregation. Patients had to indicate the quadrant of the visual field where a purely time-defined square appeared. The results showed a clear decrease in temporal resolution of patients' amblyopic eyes compared with the dominant eyes in this task. The extent of this decrease in figure-ground segregation based on time of motion onset only loosely correlated with the decrease in spatial resolution and spanned a smaller range than did the spatial loss. Control experiments with artificially induced blur in normal observers confirmed that the decrease in temporal resolution was not simply due to the acuity loss. Amblyopia not only decreases spatial resolution, but also temporal factors such as time-based figure-ground segregation, even at high stimulus contrasts. This finding suggests that the realm of neuronal processes that may be disturbed in amblyopia is larger than originally thought.

Temporal Dissociation of Striatum and Prefrontal Cortex Uncouples Anhedonia and Defense Behaviors Relevant to Depression in 6-OHDA-Lesioned Rats.

PubMed

Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Takahashi, Reinaldo N; Bertoglio, Leandro J; Cunha, Rodrigo A; Prediger, Rui D

2016-08-01

The dorsolateral striatum (DLS) processes motor and non-motor functions and undergoes extensive dopaminergic degeneration in Parkinson's disease (PD). The nigrostriatal dopaminergic degeneration also affects other brain areas including the pre-frontal cortex (PFC), which has been associated with the appearance of anhedonia and depression at pre-motor phases of PD. Using behavioral, neurochemical, and electrophysiological approaches, we investigated the temporal dissociation between the role of the DLS and PFC in the appearance of anhedonia and defense behaviors relevant to depression in rats submitted to bilateral DLS lesions with 6-hydroxydopamine (6-OHDA; 10 μg/hemisphere). 6-OHDA induced partial dopaminergic nigrostriatal damage with no gross motor impairments. Anhedonic-like behaviors were observed in the splash and sucrose consumption tests only 7 days after 6-OHDA lesion. By contrast, defense behaviors relevant to depression evaluated in the forced swimming test and social withdrawal only emerged 21 days after 6-OHDA lesion when anhedonia was no longer present. These temporally dissociated behavioral alterations were coupled to temporal- and structure-dependent alterations in dopaminergic markers such as dopamine D1 and D2 receptors and dopamine transporter, leading to altered dopamine sensitivity in DLS and PFC circuits, evaluated electrophysiologically. These results provide the first demonstration of a dissociated involvement of the DLS and PFC in anhedonic-like and defense behaviors relevant to depression in 6-OHDA-lesioned rats, which was linked with temporal fluctuations in dopaminergic receptor density, leading to altered dopaminergic system sensitivity in these two brain structures. This sheds new light to the duality between depressive and anhedonic symptoms in PD.

Alteration in 5-HT₂C, NMDA receptor and IP3 in cerebral cortex of epileptic rats: restorative role of Bacopa monnieri.

PubMed

Krishnakumar, Amee; Anju, T R; Abraham, Pretty Mary; Paulose, C S

2015-01-01

Bacopa monnieri is effective in stress management, brain function and a balanced mood. 5-HT2C receptors have been implicated in stress whereas NMDA receptors and mGlu5 play crucial role in memory and cognition. In the present study, we investigated the role of B. monnieri extract in ameliorating pilocarpine induced temporal lobe epilepsy through regulation of 5-HT2C and NMDA receptors in cerebral cortex. Our studies confirmed an increased 5-HT2C receptor function during epilepsy thereby facilitating IP3 release. We also observed an decreased NMDA receptor function with an elevated mGlu5 and GLAST gene expression in epileptic condition indicating the possibility for glutamate mediated excitotoxicity. These alterations lead to impaired behavioural functions as indicated by the Elevated Plus maze test. Carbamazepine and B. monnieri treatments to epileptic rats reversed the alterations in 5-HT2C, NMDA receptor functions and IP3 content thereby effectively managing the neurotransmitter balance in the cerebral cortex.

Spatial localization deficits and auditory cortical dysfunction in schizophrenia

PubMed Central

Perrin, Megan A.; Butler, Pamela D.; DiCostanzo, Joanna; Forchelli, Gina; Silipo, Gail; Javitt, Daniel C.

2014-01-01

Background Schizophrenia is associated with deficits in the ability to discriminate auditory features such as pitch and duration that localize to primary cortical regions. Lesions of primary vs. secondary auditory cortex also produce differentiable effects on ability to localize and discriminate free-field sound, with primary cortical lesions affecting variability as well as accuracy of response. Variability of sound localization has not previously been studied in schizophrenia. Methods The study compared performance between patients with schizophrenia (n=21) and healthy controls (n=20) on sound localization and spatial discrimination tasks using low frequency tones generated from seven speakers concavely arranged with 30 degrees separation. Results For the sound localization task, patients showed reduced accuracy (p=0.004) and greater overall response variability (p=0.032), particularly in the right hemifield. Performance was also impaired on the spatial discrimination task (p=0.018). On both tasks, poorer accuracy in the right hemifield was associated with greater cognitive symptom severity. Better accuracy in the left hemifield was associated with greater hallucination severity on the sound localization task (p=0.026), but no significant association was found for the spatial discrimination task. Conclusion Patients show impairments in both sound localization and spatial discrimination of sounds presented free-field, with a pattern comparable to that of individuals with right superior temporal lobe lesions that include primary auditory cortex (Heschl’s gyrus). Right primary auditory cortex dysfunction may protect against hallucinations by influencing laterality of functioning. PMID:20619608

Impaired mixed emotion processing in the right ventrolateral prefrontal cortex in schizophrenia: an fMRI study.

PubMed

Szabó, Ádám György; Farkas, Kinga; Marosi, Csilla; Kozák, Lajos R; Rudas, Gábor; Réthelyi, János; Csukly, Gábor

2017-12-08

Schizophrenia has a negative effect on the activity of the temporal and prefrontal cortices in the processing of emotional facial expressions. However no previous research focused on the evaluation of mixed emotions in schizophrenia, albeit they are frequently expressed in everyday situations and negative emotions are frequently expressed by mixed facial expressions. Altogether 37 subjects, 19 patients with schizophrenia and 18 healthy control subjects were enrolled in the study. The two study groups did not differ in age and education. The stimulus set consisted of 10 fearful (100%), 10 happy (100%), 10 mixed fear (70% fear and 30% happy) and 10 mixed happy facial expressions. During the fMRI acquisition pictures were presented in a randomized order and subjects had to categorize expressions by button press. A decreased activation was found in the patient group during fear, mixed fear and mixed happy processing in the right ventrolateral prefrontal cortex (VLPFC) and the right anterior insula (RAI) at voxel and cluster level after familywise error correction. No difference was found between study groups in activations to happy facial condition. Patients with schizophrenia did not show a differential activation between mixed happy and happy facial expression similar to controls in the right dorsolateral prefrontal cortex (DLPFC). Patients with schizophrenia showed decreased functioning in right prefrontal regions responsible for salience signaling and valence evaluation during emotion recognition. Our results indicate that fear and mixed happy/fear processing are impaired in schizophrenia, while happy facial expression processing is relatively intact.

SPATIAL NEGLECT AND ATTENTION NETWORKS

PubMed Central

Corbetta, Maurizio; Shulman, Gordon L.

2013-01-01

Unilateral spatial neglect is a common neurological syndrome following predominantly right hemisphere injuries to ventral fronto-parietal cortex. We propose that neglect reflects deficits in the coding of saliency, control of spatial attention, and representation within an egocentric frame of reference, in conjunction with non-spatial deficits of reorienting, target detection, and arousal/vigilance. In contrast to theories that link spatial neglect to structural damage of specific brain regions, we argue that neglect is better explained by the physiological dysfunction of distributed cortical networks. The ventral lesions in right parietal, temporal, and frontal cortex that cause neglect directly impair non-spatial functions and hypoactivate the right hemisphere, inducing abnormalities in task-evoked activity and functional connectivity of a dorsal frontal-parietal network that controls spatial attention. The anatomy and right hemisphere dominance of neglect follows from the anatomy and laterality of the ventral regions that interact with the dorsal attention network. PMID:21692662

An autopsy case of cortical superficial siderosis with persistent abnormal behavior.

PubMed

Torii, Youta; Iritani, Shuji; Fujishiro, Hiroshige; Sekiguchi, Hirotaka; Habuchi, Chikako; Umeda, Kentaro; Matsunaga, Shinji; Mimuro, Maya; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

2016-12-01

In recent years, MRI has revealed cortical superficial siderosis (cSS), which exhibits hemosiderin deposition in only the cortical surface. However, the associations between the histological findings and clinical symptoms of cSS remain unclear. We herein report an autopsy case of a 75-year-old Japanese man with cSS with persistent abnormal behavior according to cognitive impairment, hallucination and delusion. At 73 years of age, the patient presented with unusual behavior that indicated auditory hallucination and delusion. One year later, he was admitted to the hospital for malignant lymphoma. On admission, cognitive impairment was detected by a screening test. Soon after hospitalization, he presented with active delirium including visual hallucination and delusion. The patient's excited behavior was improved by the administration of a major tranquilizer. However, the abnormal behavior and cognitive impairment persisted. At 75 years of age, he died of heart failure. A neuropathological investigation revealed hemosiderin depositions in the superficial layer of the cortex in the medial and lateral frontal lobe, the lateral temporal lobe, the parietal lobe, and the medial and lateral occipital lobe. Neuritic plaques and diffuse plaques were extensively observed, which corresponded to Braak stage C and CERAD B, although NFTs were observed that corresponded to Braak stage II. Cortical amyloid angiopathy was not observed in any regions. Ischemic change of brain was also mild. Our report suggests that localized deposition of hemosiderin in the cortex might affect the manifestation of cognitive impairments and hallucination. Further clinicopathological studies are needed to clarify the clinical manifestations of patients with cSS. © 2016 Japanese Society of Neuropathology.

Reduced Gray Matter Volume in the Social Brain Network in Adults with Autism Spectrum Disorder

PubMed Central

Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Yoshimura, Sayaka; Kubota, Yasutaka; Sawada, Reiko; Sakihama, Morimitsu; Toichi, Motomi

2017-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral impairment in social interactions. Although theoretical and empirical evidence suggests that impairment in the social brain network could be the neural underpinnings of ASD, previous structural magnetic resonance imaging (MRI) studies in adults with ASD have not provided clear support for this, possibly due to confounding factors, such as language impairments. To further explore this issue, we acquired structural MRI data and analyzed gray matter volume in adults with ASD (n = 36) who had no language impairments (diagnosed with Asperger’s disorder or pervasive developmental disorder not otherwise specified, with symptoms milder than those of Asperger’s disorder), had no comorbidity, and were not taking medications, and in age- and sex-matched typically developing (TD) controls (n = 36). Univariate voxel-based morphometry analyses revealed that regional gray matter volume was lower in the ASD than in the control group in several brain regions, including the right inferior occipital gyrus, left fusiform gyrus, right middle temporal gyrus, bilateral amygdala, right inferior frontal gyrus, right orbitofrontal cortex, and left dorsomedial prefrontal cortex. A multivariate approach using a partial least squares (PLS) method showed that these regions constituted a network that could be used to discriminate between the ASD and TD groups. A PLS discriminant analysis using information from these regions showed high accuracy, sensitivity, specificity, and precision (>80%) in discriminating between the groups. These results suggest that reduced gray matter volume in the social brain network represents the neural underpinnings of behavioral social malfunctioning in adults with ASD. PMID:28824399

Auditory Cortex Is Required for Fear Potentiation of Gap Detection

PubMed Central

Weible, Aldis P.; Liu, Christine; Niell, Cristopher M.

2014-01-01

Auditory cortex is necessary for the perceptual detection of brief gaps in noise, but is not necessary for many other auditory tasks such as frequency discrimination, prepulse inhibition of startle responses, or fear conditioning with pure tones. It remains unclear why auditory cortex should be necessary for some auditory tasks but not others. One possibility is that auditory cortex is causally involved in gap detection and other forms of temporal processing in order to associate meaning with temporally structured sounds. This predicts that auditory cortex should be necessary for associating meaning with gaps. To test this prediction, we developed a fear conditioning paradigm for mice based on gap detection. We found that pairing a 10 or 100 ms gap with an aversive stimulus caused a robust enhancement of gap detection measured 6 h later, which we refer to as fear potentiation of gap detection. Optogenetic suppression of auditory cortex during pairing abolished this fear potentiation, indicating that auditory cortex is critically involved in associating temporally structured sounds with emotionally salient events. PMID:25392510

Voxel-wise resting-state MEG source magnitude imaging study reveals neurocircuitry abnormality in active-duty service members and veterans with PTSD

PubMed Central

Huang, Ming-Xiong; Yurgil, Kate A.; Robb, Ashley; Angeles, Annemarie; Diwakar, Mithun; Risbrough, Victoria B.; Nichols, Sharon L.; McLay, Robert; Theilmann, Rebecca J.; Song, Tao; Huang, Charles W.; Lee, Roland R.; Baker, Dewleen G.

2014-01-01

Post-traumatic stress disorder (PTSD) is a leading cause of sustained impairment, distress, and poor quality of life in military personnel, veterans, and civilians. Indirect functional neuroimaging studies using PET or fMRI with fear-related stimuli support a PTSD neurocircuitry model that includes amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC). However, it is not clear if this model can fully account for PTSD abnormalities detected directly by electromagnetic-based source imaging techniques in resting-state. The present study examined resting-state magnetoencephalography (MEG) signals in 25 active-duty service members and veterans with PTSD and 30 healthy volunteers. In contrast to the healthy volunteers, individuals with PTSD showed: 1) hyperactivity from amygdala, hippocampus, posterolateral orbitofrontal cortex (OFC), dorsomedial prefrontal cortex (dmPFC), and insular cortex in high-frequency (i.e., beta, gamma, and high-gamma) bands; 2) hypoactivity from vmPFC, Frontal Pole (FP), and dorsolateral prefrontal cortex (dlPFC) in high-frequency bands; 3) extensive hypoactivity from dlPFC, FP, anterior temporal lobes, precuneous cortex, and sensorimotor cortex in alpha and low-frequency bands; and 4) in individuals with PTSD, MEG activity in the left amygdala and posterolateral OFC correlated positively with PTSD symptom scores, whereas MEG activity in vmPFC and precuneous correlated negatively with symptom score. The present study showed that MEG source imaging technique revealed new abnormalities in the resting-state electromagnetic signals from the PTSD neurocircuitry. Particularly, posterolateral OFC and precuneous may play important roles in the PTSD neurocircuitry model. PMID:25180160

Sentence processing and verbal working memory in a white-matter-disconnection patient.

PubMed

Meyer, Lars; Cunitz, Katrin; Obleser, Jonas; Friederici, Angela D

2014-08-01

The Arcuate Fasciculus/Superior Longitudinal Fasciculus (AF/SLF) is the white-matter bundle that connects posterior superior temporal and inferior frontal cortex. Its causal functional role in sentence processing and verbal working memory is currently under debate. While impairments of sentence processing and verbal working memory often co-occur in patients suffering from AF/SLF damage, it is unclear whether these impairments result from shared white-matter damage to the verbal-working-memory network. The present study sought to specify the behavioral consequences of focal AF/SLF damage for sentence processing and verbal working memory, which were assessed in a single patient suffering from a cleft-like lesion spanning the deep left superior temporal gyrus, sparing most surrounding gray matter. While tractography suggests that the ventral fronto-temporal white-matter bundle is intact in this patient, the AF/SLF was not visible to tractography. In line with the hypothesis that the AF/SLF is causally involved in sentence processing, the patient׳s performance was selectively impaired on sentences that jointly involve both complex word orders and long word-storage intervals. However, the patient was unimpaired on sentences that only involved long word-storage intervals without involving complex word orders. On the contrary, the patient performed generally worse than a control group across standard verbal-working-memory tests. We conclude that the AF/SLF not only plays a causal role in sentence processing, linking regions of the left dorsal inferior frontal gyrus to the temporo-parietal region, but moreover plays a crucial role in verbal working memory, linking regions of the left ventral inferior frontal gyrus to the left temporo-parietal region. Together, the specific sentence-processing impairment and the more general verbal-working-memory impairment may imply that the AF/SLF subserves both sentence processing and verbal working memory, possibly pointing to the AF and SLF respectively supporting each. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impaired pitch perception and memory in congenital amusia: the deficit starts in the auditory cortex.

PubMed

Albouy, Philippe; Mattout, Jérémie; Bouet, Romain; Maby, Emmanuel; Sanchez, Gaëtan; Aguera, Pierre-Emmanuel; Daligault, Sébastien; Delpuech, Claude; Bertrand, Olivier; Caclin, Anne; Tillmann, Barbara

2013-05-01

Congenital amusia is a lifelong disorder of music perception and production. The present study investigated the cerebral bases of impaired pitch perception and memory in congenital amusia using behavioural measures, magnetoencephalography and voxel-based morphometry. Congenital amusics and matched control subjects performed two melodic tasks (a melodic contour task and an easier transposition task); they had to indicate whether sequences of six tones (presented in pairs) were the same or different. Behavioural data indicated that in comparison with control participants, amusics' short-term memory was impaired for the melodic contour task, but not for the transposition task. The major finding was that pitch processing and short-term memory deficits can be traced down to amusics' early brain responses during encoding of the melodic information. Temporal and frontal generators of the N100m evoked by each note of the melody were abnormally recruited in the amusic brain. Dynamic causal modelling of the N100m further revealed decreased intrinsic connectivity in both auditory cortices, increased lateral connectivity between auditory cortices as well as a decreased right fronto-temporal backward connectivity in amusics relative to control subjects. Abnormal functioning of this fronto-temporal network was also shown during the retention interval and the retrieval of melodic information. In particular, induced gamma oscillations in right frontal areas were decreased in amusics during the retention interval. Using voxel-based morphometry, we confirmed morphological brain anomalies in terms of white and grey matter concentration in the right inferior frontal gyrus and the right superior temporal gyrus in the amusic brain. The convergence between functional and structural brain differences strengthens the hypothesis of abnormalities in the fronto-temporal pathway of the amusic brain. Our data provide first evidence of altered functioning of the auditory cortices during pitch perception and memory in congenital amusia. They further support the hypothesis that in neurodevelopmental disorders impacting high-level functions (here musical abilities), abnormalities in cerebral processing can be observed in early brain responses.

Altered Whole-Brain Structural Covariance of the Hippocampal Subfields in Subcortical Vascular Mild Cognitive Impairment and Amnestic Mild Cognitive Impairment Patients.

PubMed

Wang, Xuetong; Yu, Yang; Zhao, Weina; Li, Qiongling; Li, Xinwei; Li, Shuyu; Yin, Changhao; Han, Ying

2018-01-01

The hippocampus plays important roles in memory processing. However, the hippocampus is not a homogeneous structure, which consists of several subfields. The hippocampal subfields are differently affected by many neurodegenerative diseases, especially mild cognitive impairment (MCI). Amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) are the two subtypes of MCI. aMCI is characterized by episodic memory loss, and svMCI is characterized by extensive white matter hyperintensities and multiple lacunar infarctions on magnetic resonance imaging. The primary cognitive impairment in svMCI is executive function, attention, and semantic memory. Some variations or disconnections within specific large-scale brain networks have been observed in aMCI and svMCI patients. The aim of this study was to investigate abnormalities in structural covariance networks (SCNs) between hippocampal subfields and the whole cerebral cortex in aMCI and svMCI patients, and whether these abnormalities are different between the two groups. Automated segmentation of hippocampal subfields was performed with FreeSurfer 5.3, and we selected five hippocampal subfields as the seeds of SCN analysis: CA1, CA2/3, CA4/dentate gyrus (DG), subiculum, and presubiculum. SCNs were constructed based on these hippocampal subfield seeds for each group. Significant correlations between hippocampal subfields, fusiform gyrus (FFG), and entorhinal cortex (ERC) in gray matter volume were found in each group. We also compared the differences in the strength of structural covariance between any two groups. In the aMCI group, compared to the normal controls (NC) group, we observed an increased association between the left CA1/CA4/DG/subiculum and the left temporal pole. Additionally, the hippocampal subfields (bilateral CA1, left CA2/3) significantly covaried with the orbitofrontal cortex in the svMCI group compared to the NC group. In the aMCI group compared to the svMCI group, we observed decreased association between hippocampal subfields and the right FFG, while we also observed an increased association between the bilateral subiculum/presubiculum and bilateral ERC. These findings provide new evidence that there is altered whole-brain structural covariance of the hippocampal subfields in svMCI and aMCI patients and provide insights to the pathological mechanisms of different MCI subtypes.

Psychophysical and neuroimaging responses to moving stimuli in a patient with the Riddoch phenomenon due to bilateral visual cortex lesions.

PubMed

Arcaro, Michael J; Thaler, Lore; Quinlan, Derek J; Monaco, Simona; Khan, Sarah; Valyear, Kenneth F; Goebel, Rainer; Dutton, Gordon N; Goodale, Melvyn A; Kastner, Sabine; Culham, Jody C

2018-05-09

Patients with injury to early visual cortex or its inputs can display the Riddoch phenomenon: preserved awareness for moving but not stationary stimuli. We provide a detailed case report of a patient with the Riddoch phenomenon, MC. MC has extensive bilateral lesions to occipitotemporal cortex that include most early visual cortex and complete blindness in visual field perimetry testing with static targets. Nevertheless, she shows a remarkably robust preserved ability to perceive motion, enabling her to navigate through cluttered environments and perform actions like catching moving balls. Comparisons of MC's structural magnetic resonance imaging (MRI) data to a probabilistic atlas based on controls reveals that MC's lesions encompass the posterior, lateral, and ventral early visual cortex bilaterally (V1, V2, V3A/B, LO1/2, TO1/2, hV4 and VO1 in both hemispheres) as well as more extensive damage to right parietal (inferior parietal lobule) and left ventral occipitotemporal cortex (VO1, PHC1/2). She shows some sparing of anterior occipital cortex, which may account for her ability to see moving targets beyond ~15 degrees eccentricity during perimetry. Most strikingly, functional and structural MRI revealed robust and reliable spared functionality of the middle temporal motion complex (MT+) bilaterally. Moreover, consistent with her preserved ability to discriminate motion direction in psychophysical testing, MC also shows direction-selective adaptation in MT+. A variety of tests did not enable us to discern whether input to MT+ was driven by her spared anterior occipital cortex or subcortical inputs. Nevertheless, MC shows rich motion perception despite profoundly impaired static and form vision, combined with clear preservation of activation in MT+, thus supporting the role of MT+ in the Riddoch phenomenon. Copyright © 2018 Elsevier Ltd. All rights reserved.

Perirhinal cortex and temporal lobe epilepsy

PubMed Central

Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

2013-01-01

The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554

[FMRI-study of speech perception impairment in post-stroke patients with sensory aphasia].

PubMed

Maĭorova, L A; Martynova, O V; Fedina, O N; Petrushevskiĭ, A G

2013-01-01

The aim of the study was to find neurophysiological correlates of the primary stage impairment of speech perception, namely phonemic discrimination, in patients with sensory aphasia after acute ischemic stroke in the left hemisphere by noninvasive method of fMRI. For this purpose we registered the fMRI-equivalent of mismatch negativity (MMN) in response to the speech phonemes--syllables "ba" and "pa" in odd-ball paradigm in 20 healthy subjects and 23 patients with post-stroke sensory aphasia. In healthy subjects active brain areas depending from the MMN contrast were observed in the superior temporal and inferior frontal gyri in the right and left hemispheres. In the group of patients there was a significant activation of the auditory cortex in the right hemisphere only, and this activation was less in a volume and intensity than in healthy subjects and correlated to the degree of preservation of speech. Thus, the method of recording fMRI equivalent of MMN is sensitive to study the speech perception impairment.

Resting-state functional connectivity in combat veterans suffering from impulsive aggression

PubMed Central

Heesink, Lieke; van Honk, Jack; Geuze, Elbert

2017-01-01

Abstract Impulsive aggression is common among military personnel after deployment and may arise because of impaired top-down regulation of the amygdala by prefrontal regions. This study sought to further explore this hypothesis via resting-state functional connectivity analyses in impulsively aggressive combat veterans. Male combat veterans with (n = 28) and without (n = 30) impulsive aggression problems underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were conducted with the following seed-regions: basolateral amygdala (BLA), centromedial amygdala, anterior cingulate cortex (ACC), and anterior insular cortex (AIC). Regions-of-interest analyses focused on the orbitofrontal cortex and periaqueductal gray, and yielded no significant results. In exploratory cluster analyses, we observed reduced functional connectivity between the (bilateral) BLA and left dorsolateral prefrontal cortex in the impulsive aggression group, relative to combat controls. This finding indicates that combat-related impulsive aggression may be marked by weakened functional connectivity between the amygdala and prefrontal regions, already in the absence of explicit emotional stimuli. Group differences in functional connectivity were also observed between the (bilateral) ACC and left cuneus, which may be related to heightened vigilance to potentially threatening visual cues, as well as between the left AIC and right temporal pole, possibly related to negative memory association in impulsive aggression. PMID:29040723

In search of an auditory engram.

PubMed

Fritz, Jonathan; Mishkin, Mortimer; Saunders, Richard C

2005-06-28

Monkeys trained preoperatively on a task designed to assess auditory recognition memory were impaired after removal of either the rostral superior temporal gyrus or the medial temporal lobe but were unaffected by lesions of the rhinal cortex. Behavioral analysis indicated that this result occurred because the monkeys did not or could not use long-term auditory recognition, and so depended instead on short-term working memory, which is unaffected by rhinal lesions. The findings suggest that monkeys may be unable to place representations of auditory stimuli into a long-term store and thus question whether the monkey's cerebral memory mechanisms in audition are intrinsically different from those in other sensory modalities. Furthermore, it raises the possibility that language is unique to humans not only because it depends on speech but also because it requires long-term auditory memory.

Individual variation in the propensity for prospective thought is associated with functional integration between visual and retrosplenial cortex.

PubMed

Villena-Gonzalez, Mario; Wang, Hao-Ting; Sormaz, Mladen; Mollo, Giovanna; Margulies, Daniel S; Jefferies, Elizabeth A; Smallwood, Jonathan

2018-02-01

It is well recognized that the default mode network (DMN) is involved in states of imagination, although the cognitive processes that this association reflects are not well understood. The DMN includes many regions that function as cortical "hubs", including the posterior cingulate/retrosplenial cortex, anterior temporal lobe and the hippocampus. This suggests that the role of the DMN in cognition may reflect a process of cortical integration. In the current study we tested whether functional connectivity from uni-modal regions of cortex into the DMN is linked to features of imaginative thought. We found that strong intrinsic communication between visual and retrosplenial cortex was correlated with the degree of social thoughts about the future. Using an independent dataset, we show that the same region of retrosplenial cortex is functionally coupled to regions of primary visual cortex as well as core regions that make up the DMN. Finally, we compared the functional connectivity of the retrosplenial cortex, with a region of medial prefrontal cortex implicated in the integration of information from regions of the temporal lobe associated with future thought in a prior study. This analysis shows that the retrosplenial cortex is preferentially coupled to medial occipital, temporal lobe regions and the angular gyrus, areas linked to episodic memory, scene construction and navigation. In contrast, the medial prefrontal cortex shows preferential connectivity with motor cortex and lateral temporal and prefrontal regions implicated in language, motor processes and working memory. Together these findings suggest that integrating neural information from visual cortex into retrosplenial cortex may be important for imagining the future and may do so by creating a mental scene in which prospective simulations play out. We speculate that the role of the DMN in imagination may emerge from its capacity to bind together distributed representations from across the cortex in a coherent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

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

Li Jinmei; Wang Xuefeng; Xi Zhiqin

2006-10-06

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in themore » temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.« less

Magnified Neural Envelope Coding Predicts Deficits in Speech Perception in Noise.

PubMed

Millman, Rebecca E; Mattys, Sven L; Gouws, André D; Prendergast, Garreth

2017-08-09

Verbal communication in noisy backgrounds is challenging. Understanding speech in background noise that fluctuates in intensity over time is particularly difficult for hearing-impaired listeners with a sensorineural hearing loss (SNHL). The reduction in fast-acting cochlear compression associated with SNHL exaggerates the perceived fluctuations in intensity in amplitude-modulated sounds. SNHL-induced changes in the coding of amplitude-modulated sounds may have a detrimental effect on the ability of SNHL listeners to understand speech in the presence of modulated background noise. To date, direct evidence for a link between magnified envelope coding and deficits in speech identification in modulated noise has been absent. Here, magnetoencephalography was used to quantify the effects of SNHL on phase locking to the temporal envelope of modulated noise (envelope coding) in human auditory cortex. Our results show that SNHL enhances the amplitude of envelope coding in posteromedial auditory cortex, whereas it enhances the fidelity of envelope coding in posteromedial and posterolateral auditory cortex. This dissociation was more evident in the right hemisphere, demonstrating functional lateralization in enhanced envelope coding in SNHL listeners. However, enhanced envelope coding was not perceptually beneficial. Our results also show that both hearing thresholds and, to a lesser extent, magnified cortical envelope coding in left posteromedial auditory cortex predict speech identification in modulated background noise. We propose a framework in which magnified envelope coding in posteromedial auditory cortex disrupts the segregation of speech from background noise, leading to deficits in speech perception in modulated background noise. SIGNIFICANCE STATEMENT People with hearing loss struggle to follow conversations in noisy environments. Background noise that fluctuates in intensity over time poses a particular challenge. Using magnetoencephalography, we demonstrate anatomically distinct cortical representations of modulated noise in normal-hearing and hearing-impaired listeners. This work provides the first link among hearing thresholds, the amplitude of cortical representations of modulated sounds, and the ability to understand speech in modulated background noise. In light of previous work, we propose that magnified cortical representations of modulated sounds disrupt the separation of speech from modulated background noise in auditory cortex. Copyright © 2017 Millman et al.

Reference frames for spatial frequency in face representation differ in the temporal visual cortex and amygdala.

PubMed

Inagaki, Mikio; Fujita, Ichiro

2011-07-13

Social communication in nonhuman primates and humans is strongly affected by facial information from other individuals. Many cortical and subcortical brain areas are known to be involved in processing facial information. However, how the neural representation of faces differs across different brain areas remains unclear. Here, we demonstrate that the reference frame for spatial frequency (SF) tuning of face-responsive neurons differs in the temporal visual cortex and amygdala in monkeys. Consistent with psychophysical properties for face recognition, temporal cortex neurons were tuned to image-based SFs (cycles/image) and showed viewing distance-invariant representation of face patterns. On the other hand, many amygdala neurons were influenced by retina-based SFs (cycles/degree), a characteristic that is useful for social distance computation. The two brain areas also differed in the luminance contrast sensitivity of face-responsive neurons; amygdala neurons sharply reduced their responses to low luminance contrast images, while temporal cortex neurons maintained the level of their responses. From these results, we conclude that different types of visual processing in the temporal visual cortex and the amygdala contribute to the construction of the neural representations of faces.

Temporal Processing Capacity in High-Level Visual Cortex Is Domain Specific.

PubMed

Stigliani, Anthony; Weiner, Kevin S; Grill-Spector, Kalanit

2015-09-09

Prevailing hierarchical models propose that temporal processing capacity--the amount of information that a brain region processes in a unit time--decreases at higher stages in the ventral stream regardless of domain. However, it is unknown if temporal processing capacities are domain general or domain specific in human high-level visual cortex. Using a novel fMRI paradigm, we measured temporal capacities of functional regions in high-level visual cortex. Contrary to hierarchical models, our data reveal domain-specific processing capacities as follows: (1) regions processing information from different domains have differential temporal capacities within each stage of the visual hierarchy and (2) domain-specific regions display the same temporal capacity regardless of their position in the processing hierarchy. In general, character-selective regions have the lowest capacity, face- and place-selective regions have an intermediate capacity, and body-selective regions have the highest capacity. Notably, domain-specific temporal processing capacities are not apparent in V1 and have perceptual implications. Behavioral testing revealed that the encoding capacity of body images is higher than that of characters, faces, and places, and there is a correspondence between peak encoding rates and cortical capacities for characters and bodies. The present evidence supports a model in which the natural statistics of temporal information in the visual world may affect domain-specific temporal processing and encoding capacities. These findings suggest that the functional organization of high-level visual cortex may be constrained by temporal characteristics of stimuli in the natural world, and this temporal capacity is a characteristic of domain-specific networks in high-level visual cortex. Significance statement: Visual stimuli bombard us at different rates every day. For example, words and scenes are typically stationary and vary at slow rates. In contrast, bodies are dynamic and typically change at faster rates. Using a novel fMRI paradigm, we measured temporal processing capacities of functional regions in human high-level visual cortex. Contrary to prevailing theories, we find that different regions have different processing capacities, which have behavioral implications. In general, character-selective regions have the lowest capacity, face- and place-selective regions have an intermediate capacity, and body-selective regions have the highest capacity. These results suggest that temporal processing capacity is a characteristic of domain-specific networks in high-level visual cortex and contributes to the segregation of cortical regions. Copyright © 2015 the authors 0270-6474/15/3512412-13$15.00/0.

Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

PubMed

Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

2015-02-01

Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

[CADASIL with cysteine-sparing NOTCH3 mutation manifesting as dissociated progression between cognitive impairment and brain image findings in 3 years: A case report].

PubMed

Tachiyama, Keisuke; Shiga, Yuji; Shimoe, Yutaka; Mizuta, Ikuko; Mizuno, Toshiki; Kuriyama, Masaru

2018-04-25

A 55-year-old man with no history of stroke or migraine presented to the clinic with cognitive impairment and depression that had been experiencing for two years. Neurological examination showed bilateral pyramidal signs, and impairments in cognition and attention. Brain MRI revealed multiple lacunar lesions and microbleeds in the deep cerebral white matter, subcortical regions, and brainstem, as well as diffuse white matter hyperintensities without anterior temporal pole involvement. Cerebral single-photon emission computed tomography (SPECT) revealed bilateral hypoperfusion in the basal ganglia. Gene analysis revealed an arginine-to-proline missense mutation in the NOTCH3 gene at codon 75. The patient was administered lomerizine (10 mg/day), but the patient's cognitive impairment and cerebral atrophy continued to worsen. Follow-up testing with MRI three years after his initial diagnosis revealed similar lacunar infarctions, cerebral microbleeds, and diffuse white matter hyperintensities to those observed three years earlier. However, MRI scans revealed signs of increased cerebral blood flow. Together, these findings suggest that the patient's cognitive impairments may have been caused by pathogenesis in the cerebral cortex.

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats

PubMed Central

Wen, Tong-Chun; Lall, Sophia; Pagnotta, Corey; Markward, James; Gupta, Disha; Ratnadurai-Giridharan, Shivakeshavan; Bucci, Jacqueline; Greenwald, Lucy; Klugman, Madelyne; Hill, N. Jeremy; Carmel, Jason B.

2018-01-01

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy. PMID:29706871

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

PubMed

Wen, Tong-Chun; Lall, Sophia; Pagnotta, Corey; Markward, James; Gupta, Disha; Ratnadurai-Giridharan, Shivakeshavan; Bucci, Jacqueline; Greenwald, Lucy; Klugman, Madelyne; Hill, N Jeremy; Carmel, Jason B

2018-01-01

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy.

Brain activity related to working memory for temporal order and object information.

PubMed

Roberts, Brooke M; Libby, Laura A; Inhoff, Marika C; Ranganath, Charan

2017-06-08

Maintaining items in an appropriate sequence is important for many daily activities; however, remarkably little is known about the neural basis of human temporal working memory. Prior work suggests that the prefrontal cortex (PFC) and medial temporal lobe (MTL), including the hippocampus, play a role in representing information about temporal order. The involvement of these areas in successful temporal working memory, however, is less clear. Additionally, it is unknown whether regions in the PFC and MTL support temporal working memory across different timescales, or at coarse or fine levels of temporal detail. To address these questions, participants were scanned while completing 3 working memory task conditions (Group, Position and Item) that were matched in terms of difficulty and the number of items to be actively maintained. Group and Position trials probed temporal working memory processes, requiring the maintenance of hierarchically organized coarse and fine temporal information, respectively. To isolate activation related to temporal working memory, Group and Position trials were contrasted against Item trials, which required detailed working memory maintenance of visual objects. Results revealed that working memory encoding and maintenance of temporal information relative to visual information was associated with increased activation in dorsolateral PFC (DLPFC), and perirhinal cortex (PRC). In contrast, maintenance of visual details relative to temporal information was characterized by greater activation of parahippocampal cortex (PHC), medial and anterior PFC, and retrosplenial cortex. In the hippocampus, a dissociation along the longitudinal axis was observed such that the anterior hippocampus was more active for working memory encoding and maintenance of visual detail information relative to temporal information, whereas the posterior hippocampus displayed the opposite effect. Posterior parietal cortex was the only region to show sensitivity to temporal working memory across timescales, and was particularly involved in the encoding and maintenance of fine temporal information relative to maintenance of temporal information at more coarse timescales. Collectively, these results highlight the involvement of PFC and MTL in temporal working memory processes, and suggest a dissociation in the type of working memory information represented along the longitudinal axis of the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Task-dependent modulation of regions in the left temporal cortex during auditory sentence comprehension.

PubMed

Zhang, Linjun; Yue, Qiuhai; Zhang, Yang; Shu, Hua; Li, Ping

2015-01-01

Numerous studies have revealed the essential role of the left lateral temporal cortex in auditory sentence comprehension along with evidence of the functional specialization of the anterior and posterior temporal sub-areas. However, it is unclear whether task demands (e.g., active vs. passive listening) modulate the functional specificity of these sub-areas. In the present functional magnetic resonance imaging (fMRI) study, we addressed this issue by applying both independent component analysis (ICA) and general linear model (GLM) methods. Consistent with previous studies, intelligible sentences elicited greater activity in the left lateral temporal cortex relative to unintelligible sentences. Moreover, responses to intelligibility in the sub-regions were differentially modulated by task demands. While the overall activation patterns of the anterior and posterior superior temporal sulcus and middle temporal gyrus (STS/MTG) were equivalent during both passive and active tasks, a middle portion of the STS/MTG was found to be selectively activated only during the active task under a refined analysis of sub-regional contributions. Our results not only confirm the critical role of the left lateral temporal cortex in auditory sentence comprehension but further demonstrate that task demands modulate functional specialization of the anterior-middle-posterior temporal sub-areas. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neural representations of faces and body parts in macaque and human cortex: a comparative FMRI study.

PubMed

Pinsk, Mark A; Arcaro, Michael; Weiner, Kevin S; Kalkus, Jan F; Inati, Souheil J; Gross, Charles G; Kastner, Sabine

2009-05-01

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas.

Neural Representations of Faces and Body Parts in Macaque and Human Cortex: A Comparative fMRI Study

PubMed Central

Pinsk, Mark A.; Arcaro, Michael; Weiner, Kevin S.; Kalkus, Jan F.; Inati, Souheil J.; Gross, Charles G.; Kastner, Sabine

2009-01-01

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part–selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part–selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas. PMID:19225169

Localization of Impaired Kinesthetic Processing Post-stroke.

PubMed

Kenzie, Jeffrey M; Semrau, Jennifer A; Findlater, Sonja E; Yu, Amy Y; Desai, Jamsheed A; Herter, Troy M; Hill, Michael D; Scott, Stephen H; Dukelow, Sean P

2016-01-01

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects ( N = 142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects' ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects' mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with damage to the right supramarginal gyrus. These results suggest that processing of kinesthetic information occurs beyond traditional sensorimotor areas. Additionally, this dissociation between kinesthetic sub-components may indicate specialized processing in these brain areas that form a larger distributed network.

Localization of Impaired Kinesthetic Processing Post-stroke

PubMed Central

Kenzie, Jeffrey M.; Semrau, Jennifer A.; Findlater, Sonja E.; Yu, Amy Y.; Desai, Jamsheed A.; Herter, Troy M.; Hill, Michael D.; Scott, Stephen H.; Dukelow, Sean P.

2016-01-01

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects (N = 142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects' ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects' mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with damage to the right supramarginal gyrus. These results suggest that processing of kinesthetic information occurs beyond traditional sensorimotor areas. Additionally, this dissociation between kinesthetic sub-components may indicate specialized processing in these brain areas that form a larger distributed network. PMID:27799902

Different macaque models of cognitive aging exhibit task-dependent behavioral disparities.

PubMed

Comrie, Alison E; Gray, Daniel T; Smith, Anne C; Barnes, Carol A

2018-05-15

Deficits in cognitive functions that rely on the integrity of the frontal and temporal lobes are characteristic of normative human aging. Due to similar aging phenotypes and homologous cortical organization between nonhuman primates and humans, several species of macaque monkeys are used as models to explore brain senescence. These macaque species are typically regarded as equivalent models of cognitive aging, yet no direct comparisons have been made to support this assumption. Here we used adult and aged rhesus and bonnet macaques (Macaca mulatta and Macaca radiata) to characterize the effect of age on acquisition and retention of information across delays in a battery of behavioral tasks that rely on prefrontal cortex and medial temporal lobe networks. The cognitive functions that were tested include visuospatial short-term memory, object recognition memory, and object-reward association memory. In general, bonnet macaques at all ages outperformed rhesus macaques on tasks thought to rely primarily on the prefrontal cortex, and were more resilient to age-related deficits in these behaviors. On the other hand, both species were comparably impaired by age on tasks thought to preferentially engage the medial temporal lobe. Together, these results suggest that rhesus and bonnet macaques are not equivalent models of cognitive aging and highlight the value of cross-species comparisons. These observations should enable improved design and interpretation of future experiments aimed at understanding changes in cognition across the lifespan. Copyright © 2018 Elsevier B.V. All rights reserved.

Spectral context affects temporal processing in awake auditory cortex

PubMed Central

Beitel, Ralph E.; Vollmer, Maike; Heiser, Marc A; Schreiner, Christoph E.

2013-01-01

Amplitude modulation encoding is critical for human speech perception and complex sound processing in general. The modulation transfer function (MTF) is a staple of auditory psychophysics, and has been shown to predict speech intelligibility performance in a range of adverse listening conditions and hearing impairments, including cochlear implant-supported hearing. Although both tonal and broadband carriers have been employed in psychophysical studies of modulation detection and discrimination, relatively little is known about differences in the cortical representation of such signals. We obtained MTFs in response to sinusoidal amplitude modulation (SAM) for both narrowband tonal carriers and 2-octave bandwidth noise carriers in the auditory core of awake squirrel monkeys. MTFs spanning modulation frequencies from 4 to 512 Hz were obtained using 16 channel linear recording arrays sampling across all cortical laminae. Carrier frequency for tonal SAM and center frequency for noise SAM was set at the estimated best frequency for each penetration. Changes in carrier type affected both rate and temporal MTFs in many neurons. Using spike discrimination techniques, we found that discrimination of modulation frequency was significantly better for tonal SAM than for noise SAM, though the differences were modest at the population level. Moreover, spike trains elicited by tonal and noise SAM could be readily discriminated in most cases. Collectively, our results reveal remarkable sensitivity to the spectral content of modulated signals, and indicate substantial interdependence between temporal and spectral processing in neurons of the core auditory cortex. PMID:23719811

White matter integrity and cognition in Parkinson's disease: a cross-sectional study

PubMed Central

Auning, Eirik; Kjærvik, Veslemøy Krohn; Selnes, Per; Aarsland, Dag; Haram, Astrid; Bjørnerud, Atle; Hessen, Erik; Esnaashari, Abdolreza; Fladby, Tormod

2014-01-01

Objective We used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinson’s disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimer’s disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance. Methods This study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group. Results Patients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities. Conclusions In early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD. PMID:24448846

The origins of originality: the neural bases of creative thinking and originality.

PubMed

Shamay-Tsoory, S G; Adler, N; Aharon-Peretz, J; Perry, D; Mayseless, N

2011-01-01

Although creativity has been related to prefrontal activity, recent neurological case studies postulate that patients who have left frontal and temporal degeneration involving deterioration of language abilities may actually develop de novo artistic abilities. In this study, we propose a neural and cognitive model according to which a balance between the two hemispheres affects a major aspect of creative cognition, namely, originality. In order to examine the neural basis of originality, that is, the ability to produce statistically infrequent ideas, patients with localized lesions in the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), and posterior parietal and temporal cortex (PC), were assessed by two tasks involving divergent thinking and originality. Results indicate that lesions in the mPFC involved the most profound impairment in originality. Furthermore, precise anatomical mapping of lesions indicated that while the extent of lesion in the right mPFC was associated with impaired originality, lesions in the left PC were associated with somewhat elevated levels of originality. A positive correlation between creativity scores and left PC lesions indicated that the larger the lesion is in this area the greater the originality. On the other hand, a negative correlation was observed between originality scores and lesions in the right mPFC. It is concluded that the right mPFC is part of a right fronto-parietal network which is responsible for producing original ideas. It is possible that more linear cognitive processing such as language, mediated by left hemisphere structures interferes with creative cognition. Therefore, lesions in the left hemisphere may be associated with elevated levels of originality. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

Inactivation of the Infralimbic but Not the Prelimbic Cortex Impairs Consolidation and Retrieval of Fear Extinction

ERIC Educational Resources Information Center

Laurent, Vincent; Westbrook, R. Frederick

2009-01-01

Rats were subjected to one or two cycles of context fear conditioning and extinction to study the roles of the prelimbic cortex (PL) and infralimbic cortex (IL) in learning and relearning to inhibit fear responses. Inactivation of the PL depressed fear responses across the first or second extinction but did not impair learning or relearning fear…

Superior Temporal Activation as a Function of Linguistic Knowledge: Insights from Deaf Native Signers Who Speechread

ERIC Educational Resources Information Center

Capek, Cheryl M.; Woll, Bencie; MacSweeney, Mairead; Waters, Dafydd; McGuire, Philip K.; David, Anthony S.; Brammer, Michael J.; Campbell, Ruth

2010-01-01

Studies of spoken and signed language processing reliably show involvement of the posterior superior temporal cortex. This region is also reliably activated by observation of meaningless oral and manual actions. In this study we directly compared the extent to which activation in posterior superior temporal cortex is modulated by linguistic…

[The participation of the projection areas of the temporal cortex in the sensory support of certain forms of cognitive processes].

PubMed

Mukhin, E I; Orlova, E I; Teriaeva, N B; Mukhina, Iu K; Nabieva, T N

1993-01-01

In neuropsychophysiological and biochemical experiments was studied the role of the temporal cortex of the cat (AI, AII) in mnemonic, perceptive, gnostic functions, praxis, and the higher cognitive processes. The participation of the temporal fields in the mechanisms forming the gnostic imagery activity was shown.

Subcortical aphasia: a longitudinal PET study.

PubMed

de Boissezon, Xavier; Démonet, Jean-François; Puel, Michèle; Marie, Nathalie; Raboyeau, Gaëlle; Albucher, Jean-François; Chollet, François; Cardebat, Dominique

2005-07-01

Very few neuroimaging studies have focused on follow-up of subcortical aphasia. Here, overt language production tasks were used to correlate regional cerebral blood flow (rCBF) changes and language performance in patients with vascular subcortical lesions. Seven aphasic patients were scanned twice with positron emission tomography (PET) at 1-year interval during a word-generation task. Using SPM2, Language-Rest contrast at PET1 was correlated to language performance and to time-lag from stroke. The same contrast was performed at PET2 and session effect (PET2-PET1) was correlated with performance improvement. At PET1, correlation between rCBF and delay from stroke involved mainly ventral regions of the left temporal cortex and mesial frontal cortex. Correlations between rCBF and performance showed predominantly left dorsal regions in the frontal, temporal, and parietal lobes, but also the left ventral temporal cortex. One year apart, language performance improved and rCBF increased in perisylvian regions bilaterally. Best performers at PET2 showed an increase of activity in left ventral temporal cortex as well as in right middle temporal gyrus. On follow-up, expected language improvement and increase of activation in the classical language areas and their counterparts were observed. Moreover, all correlational analyses both at PET1 and on follow-up implicated the anterior part of the left inferior temporal gyrus, suggesting a disconnection between the superior and inferior parts of the left temporal cortex and a specific role for this region in lexical semantic processing.

Neural correlates of mirth and laughter: a direct electrical cortical stimulation study.

PubMed

Yamao, Yukihiro; Matsumoto, Riki; Kunieda, Takeharu; Shibata, Sumiya; Shimotake, Akihiro; Kikuchi, Takayuki; Satow, Takeshi; Mikuni, Nobuhiro; Fukuyama, Hidenao; Ikeda, Akio; Miyamoto, Susumu

2015-05-01

Laughter consists of both motor and emotional aspects. The emotional component, known as mirth, is usually associated with the motor component, namely, bilateral facial movements. Previous electrical cortical stimulation (ES) studies revealed that mirth was associated with the basal temporal cortex, inferior frontal cortex, and medial frontal cortex. Functional neuroimaging implicated a role for the left inferior frontal and bilateral temporal cortices in humor processing. However, the neural origins and pathways linking mirth with facial movements are still unclear. We hereby report two cases with temporal lobe epilepsy undergoing subdural electrode implantation in whom ES of the left basal temporal cortex elicited both mirth and laughter-related facial muscle movements. In one case with normal hippocampus, high-frequency ES consistently caused contralateral facial movement, followed by bilateral facial movements with mirth. In contrast, in another case with hippocampal sclerosis (HS), ES elicited only mirth at low intensity and short duration, and eventually laughter at higher intensity and longer duration. In both cases, the basal temporal language area (BTLA) was located within or adjacent to the cortex where ES produced mirth. In conclusion, the present direct ES study demonstrated that 1) mirth had a close relationship with language function, 2) intact mesial temporal structures were actively engaged in the beginning of facial movements associated with mirth, and 3) these emotion-related facial movements had contralateral dominance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessment of Extent and Role of Tau in Subcortical Vascular Cognitive Impairment Using 18F-AV1451 Positron Emission Tomography Imaging.

PubMed

Kim, Hee Jin; Park, Seongbeom; Cho, Hanna; Jang, Young Kyoung; San Lee, Jin; Jang, Hyemin; Kim, Yeshin; Kim, Ko Woon; Ryu, Young Hoon; Choi, Jae Yong; Moon, Seung Hwan; Weiner, Michael W; Jagust, William J; Rabinovici, Gil D; DeCarli, Charles; Lyoo, Chul Hyoung; Na, Duk L; Seo, Sang Won

2018-05-14

Amyloid-β (Aβ), tau, and cerebral small vessel disease (CSVD), which occasionally coexist, are the most common causes of cognitive impairments in older people. However, whether tau is observed in patients with subcortical vascular cognitive impairment (SVCI), as well as its associations with Aβ and CSVD, are not yet established. More importantly, the role of tau underlying cognitive impairments in SVCI is unknown. To investigate the extent and the role of tau in patients with SVCI using 18F-AV1451, which is a new ligand to detect neurofibrillary tangles in vivo. This cross-sectional study recruited 64 patients with SVCI from June 2015 to December 2016 at Samsung Medical Center, Seoul, Korea. The patients had significant ischemia on brain magnetic resonance imaging, defined as periventricular white matter hyperintensity at least 10 mm and deep white matter hyperintensity at least 25 mm. We excluded 3 patients with SVCI owing to segmentation error during AV1451 positron emission tomography analysis. We calculated CSVD scores based on the volumes of white matter hyperintensities, numbers of lacunes, and microbleeds using magnetic resonance imaging data. The presence of Aβ was assessed using fluorine 18-labeled (18F) florbetaben positron emission tomography. Tau was measured using 18F-AV1451 positron emission tomography. We determined the spreading order of tau by sorting the regional frequencies of cortical involvement. We evaluated the complex associations between Aβ, CSVD, AV1451 uptake, and cognition in patients with SVCI. Of the 61 patients with SVCI, 44 (72.1%) were women and the mean (SD) age was 78.7 (6.3) years. Patients with SVCI, especially patients with Aβ-negative SVCI, showed higher AV1451 uptake in the inferior temporal areas compared with normal control individuals. In patients with SVCI, Aβ positivity and CSVD score were each independently associated with increased AV1451 uptake in the medial temporal and inferior temporal regions, respectively. Involvement frequency of AV1451 uptake in the fusiform gyrus, inferior temporal, and precuneus regions were higher than that in the parahippocampal region. In patients with SVCI, higher AV1451 uptake in the inferior temporal and medial temporal regions correlated with worse language and general cognitive function. In patients with SVCI, Aβ positivity and CSVD score each correlated with worse general cognitive function, which was completely mediated by AV1451 uptake in the entorhinal cortex and inferior temporal gyrus, respectively. Our findings suggest that in SVCI, both Aβ and CSVD were independently associated with increased tau accumulation. Furthermore, tau burden played a pivotal role because it was the final common pathway for the cognitive impairment in patients with SVCI.

The role of human ventral visual cortex in motion perception

PubMed Central

Saygin, Ayse P.; Lorenzi, Lauren J.; Egan, Ryan; Rees, Geraint; Behrmann, Marlene

2013-01-01

Visual motion perception is fundamental to many aspects of visual perception. Visual motion perception has long been associated with the dorsal (parietal) pathway and the involvement of the ventral ‘form’ (temporal) visual pathway has not been considered critical for normal motion perception. Here, we evaluated this view by examining whether circumscribed damage to ventral visual cortex impaired motion perception. The perception of motion in basic, non-form tasks (motion coherence and motion detection) and complex structure-from-motion, for a wide range of motion speeds, all centrally displayed, was assessed in five patients with a circumscribed lesion to either the right or left ventral visual pathway. Patients with a right, but not with a left, ventral visual lesion displayed widespread impairments in central motion perception even for non-form motion, for both slow and for fast speeds, and this held true independent of the integrity of areas MT/V5, V3A or parietal regions. In contrast with the traditional view in which only the dorsal visual stream is critical for motion perception, these novel findings implicate a more distributed circuit in which the integrity of the right ventral visual pathway is also necessary even for the perception of non-form motion. PMID:23983030

Social cognition and prefrontal hemodynamic responses during a working memory task in schizophrenia.

PubMed

Pu, Shenghong; Nakagome, Kazuyuki; Yamada, Takeshi; Itakura, Masashi; Yamanashi, Takehiko; Yamada, Sayaka; Masai, Mieko; Miura, Akihiko; Yamauchi, Takahira; Satake, Takahiro; Iwata, Masaaki; Nagata, Izumi; Roberts, David L; Kaneko, Koichi

2016-03-01

Social cognition is an important determinant of functional impairment in schizophrenia, but its relationship with the prefrontal functional abnormalities associated with the condition is still unclear. The present study aimed to explore the relationship between social cognition and prefrontal function in patients with schizophrenia using 52-channel near-infrared spectroscopy (NIRS). Twenty-six patients with schizophrenia and 26 age-, gender-, and intelligence quotient-matched healthy controls (HCs) participated in the study. Hemodynamic responses in the prefrontal and superior temporal cortical regions were assessed during a working memory task using NIRS. Social cognition was assessed using the Social Cognition Screening Questionnaire (SCSQ). The observed hemodynamic responses were significantly reduced in the lateral prefrontal cortex (PFC), the frontopolar cortex, and temporal regions in subjects with schizophrenia compared to HCs. Additionally, lateral PFC hemodynamic responses assessed during the working memory task demonstrated a strong positive correlation with the SCSQ theory of mind (ToM) subscale score even after controlling for working memory performance. These results suggest that ToM integrity is closely related to lateral PFC functional abnormalities found in patients with schizophrenia. In addition, this study provides evidence to suggest that NIRS could be used to identify biomarkers of social cognition function in subjects with schizophrenia.

The structural neuroanatomy of music emotion recognition: Evidence from frontotemporal lobar degeneration

PubMed Central

Omar, Rohani; Henley, Susie M.D.; Bartlett, Jonathan W.; Hailstone, Julia C.; Gordon, Elizabeth; Sauter, Disa A.; Frost, Chris; Scott, Sophie K.; Warren, Jason D.

2011-01-01

Despite growing clinical and neurobiological interest in the brain mechanisms that process emotion in music, these mechanisms remain incompletely understood. Patients with frontotemporal lobar degeneration (FTLD) frequently exhibit clinical syndromes that illustrate the effects of breakdown in emotional and social functioning. Here we investigated the neuroanatomical substrate for recognition of musical emotion in a cohort of 26 patients with FTLD (16 with behavioural variant frontotemporal dementia, bvFTD, 10 with semantic dementia, SemD) using voxel-based morphometry. On neuropsychological evaluation, patients with FTLD showed deficient recognition of canonical emotions (happiness, sadness, anger and fear) from music as well as faces and voices compared with healthy control subjects. Impaired recognition of emotions from music was specifically associated with grey matter loss in a distributed cerebral network including insula, orbitofrontal cortex, anterior cingulate and medial prefrontal cortex, anterior temporal and more posterior temporal and parietal cortices, amygdala and the subcortical mesolimbic system. This network constitutes an essential brain substrate for recognition of musical emotion that overlaps with brain regions previously implicated in coding emotional value, behavioural context, conceptual knowledge and theory of mind. Musical emotion recognition may probe the interface of these processes, delineating a profile of brain damage that is essential for the abstraction of complex social emotions. PMID:21385617

Medial prefrontal cortex lesions in the female rat affect sexual and maternal behavior and their sequential organization.

PubMed

Afonso, Veronica M; Sison, Margarette; Lovic, Vedran; Fleming, Alison S

2007-06-01

Temporal sequences of sexual and maternal behaviors in female rats and their correlation with each other and with performance on a sensory-motor gating response inhibition task assessed by prepulse inhibition (PPI) were investigated following medial prefrontal cortex (mPFC) lesions. Following excitotoxic mPFC (n = 10) or sham (n = 9) lesions, sexual behaviors across the ovarian cycle were scored. After mating and parturition, maternal interactions were scored until pups reached postnatal Day 10. After resumption of the ovarian cycle, the female rats were tested for PPI. Compared with sham lesions, mPFC lesions impaired proceptive behaviors and some maternal behaviors (e.g., pup retrieval, pup licking) but did not affect others (e.g., nest building, pup mouthing). Lesions disrupted temporal sequences of solicitations (number of male orientations followed, within 4 s, by a level change) and pup retrievals (number of pup retrievals followed, within 5 s, by another retrieval). These sequential behavior patterns were significantly correlated with each other and with PPI. However, when PPI effects were partialled out, group differences were less strong, but persisted. This study demonstrated that mPFC manipulations affect actions rich in sequential structure in response to biologically relevant stimuli. Copyright (c) 2007 APA, all rights reserved.

Temporal plasticity in auditory cortex improves neural discrimination of speech sounds

PubMed Central

Engineer, Crystal T.; Shetake, Jai A.; Engineer, Navzer D.; Vrana, Will A.; Wolf, Jordan T.; Kilgard, Michael P.

2017-01-01

Background Many individuals with language learning impairments exhibit temporal processing deficits and degraded neural responses to speech sounds. Auditory training can improve both the neural and behavioral deficits, though significant deficits remain. Recent evidence suggests that vagus nerve stimulation (VNS) paired with rehabilitative therapies enhances both cortical plasticity and recovery of normal function. Objective/Hypothesis We predicted that pairing VNS with rapid tone trains would enhance the primary auditory cortex (A1) response to unpaired novel speech sounds. Methods VNS was paired with tone trains 300 times per day for 20 days in adult rats. Responses to isolated speech sounds, compressed speech sounds, word sequences, and compressed word sequences were recorded in A1 following the completion of VNS-tone train pairing. Results Pairing VNS with rapid tone trains resulted in stronger, faster, and more discriminable A1 responses to speech sounds presented at conversational rates. Conclusion This study extends previous findings by documenting that VNS paired with rapid tone trains altered the neural response to novel unpaired speech sounds. Future studies are necessary to determine whether pairing VNS with appropriate auditory stimuli could potentially be used to improve both neural responses to speech sounds and speech perception in individuals with receptive language disorders. PMID:28131520

The structural neuroanatomy of music emotion recognition: evidence from frontotemporal lobar degeneration.

PubMed

Omar, Rohani; Henley, Susie M D; Bartlett, Jonathan W; Hailstone, Julia C; Gordon, Elizabeth; Sauter, Disa A; Frost, Chris; Scott, Sophie K; Warren, Jason D

2011-06-01

Despite growing clinical and neurobiological interest in the brain mechanisms that process emotion in music, these mechanisms remain incompletely understood. Patients with frontotemporal lobar degeneration (FTLD) frequently exhibit clinical syndromes that illustrate the effects of breakdown in emotional and social functioning. Here we investigated the neuroanatomical substrate for recognition of musical emotion in a cohort of 26 patients with FTLD (16 with behavioural variant frontotemporal dementia, bvFTD, 10 with semantic dementia, SemD) using voxel-based morphometry. On neuropsychological evaluation, patients with FTLD showed deficient recognition of canonical emotions (happiness, sadness, anger and fear) from music as well as faces and voices compared with healthy control subjects. Impaired recognition of emotions from music was specifically associated with grey matter loss in a distributed cerebral network including insula, orbitofrontal cortex, anterior cingulate and medial prefrontal cortex, anterior temporal and more posterior temporal and parietal cortices, amygdala and the subcortical mesolimbic system. This network constitutes an essential brain substrate for recognition of musical emotion that overlaps with brain regions previously implicated in coding emotional value, behavioural context, conceptual knowledge and theory of mind. Musical emotion recognition may probe the interface of these processes, delineating a profile of brain damage that is essential for the abstraction of complex social emotions. Copyright © 2011 Elsevier Inc. All rights reserved.

Two-Stage Processing of Aesthetic Information in the Human Brain Revealed by Neural Adaptation Paradigm.

PubMed

Iwasaki, Miho; Noguchi, Yasuki; Kakigi, Ryusuke

2018-06-07

Some researchers in aesthetics assume visual features related to aesthetic perception (e.g. golden ratio and symmetry) commonly embedded in masterpieces. If this is true, an intriguing hypothesis is that the human brain has neural circuitry specialized for the processing of visual beauty. We presently tested this hypothesis by combining a neuroimaging technique with the repetition suppression (RS) paradigm. Subjects (non-experts in art) viewed two images of sculptures sequentially presented. Some sculptures obeyed the golden ratio (canonical images), while the golden proportion were impaired in other sculptures (deformed images). We found that the occipito-temporal cortex in the right hemisphere showed the RS when a canonical sculpture (e.g. Venus de Milo) was repeatedly presented, but not when its deformed version was repeated. Furthermore, the right parietal cortex showed the RS to the canonical proportion even when two sculptures had different identities (e.g. Venus de Milo as the first stimulus and David di Michelangelo as the second), indicating that this region encodes the golden ratio as an abstract rule shared by different sculptures. Those results suggest two separate stages of neural processing for aesthetic information (one in the occipito-temporal and another in the parietal regions) that are hierarchically arranged in the human brain.

Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept.

PubMed

Romanova, G A; Shakova, F M; Gudasheva, T A; Ostrovskaya, R U

2002-12-01

Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.

Interaction among subsystems within default mode network diminished in schizophrenia patients: a dynamic connectivity approach

PubMed Central

Du, Yuhui; Pearlson, Godfrey D; Yu, Qingbao; He, Hao; Lin, Dongdong; Sui, Jing; Wu, Lei; Calhoun, Vince D.

2015-01-01

Default mode network (DMN) has been reported altered in schizophrenia (SZ) using static connectivity analysis. However, the studies on dynamic characteristics of DMN in SZ are still limited. In this work, we compare dynamic connectivity within DMN between 82 healthy controls (HC) and 82 SZ patients using resting-state fMRI. Firstly, dynamic DMN was computed using a sliding time window method for each subject. Then, the overall connectivity strengths were compared between two groups. Furthermore, we estimated functional connectivity states using K-means clustering, and then investigated group differences with respect to the connectivity strengths in states, the dwell time in each state, and the transition times between states. Finally, graph metrics of time-varying connectivity patterns and connectivity states were assessed. Results suggest that measured by the overall connectivity, HC showed stronger inter-subsystem interaction than patients. Compared to HC, patients spent less time in the states with nodes tightly connected. For each state, SZ patients presented relatively weaker connectivity strengths mainly in inter-subsystem. Patients also exhibited lower values in averaged node strength, clustering coefficient, global efficiency, and local efficiency than HC. In summary, our findings indicate that SZ showed impaired interaction among DMN subsystems, with a reduced central role for posterior cingulate cortex (PCC) and anterior medial prefrontal cortex (aMPFC) hubs as well as weaker interaction between dorsal medial prefrontal cortex (dMPFC) subsystem and medial temporal lobe (MTL) subsystem. For SZ, decreased integration of DMN may be associated with impaired ability in making self-other distinctions and coordinating present mental states with episodic decisions about future. PMID:26654933

Brain Correlates of Self-Evaluation Deficits in Schizophrenia: A Combined Functional and Structural MRI Study

PubMed Central

Fan, Fengmei; Zou, Yizhuang; Jin, Zhen; Zen, Yawei; Zhu, Xiaolin; Yang, Fude; Tan, Yunlong; Zhou, Dongfeng

2015-01-01

Self-evaluation plays an important role in adaptive functioning and is a process that is typically impaired in patients with schizophrenia. Underlying neural mechanisms for this dysfunction may be associated with manifested psychosis. However, the brain substrates underlying this deficit are not well known. The present study used brain blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and gray matter voxel-based morphometry to explore the functional and structural brain correlates of self-evaluation deficits in schizophrenia. Eighteen patients with schizophrenia and 17 healthy controls were recruited and asked to judge whether a set of personality-trait adjectives were appropriate for describing themselves, a familiar other, or whether the adjectives were of positive or negative valence. Patients had slower response times for negative trait attributions than controls did; responses to positive trait attributions were faster than those for negative traits among the patient group, while no differences were observed in the control group. Control subjects showed greater activation within the dorsal medial prefrontal cortex (dMPFC) and the anterior cingulate cortex (ACC) than the patient group during the self-evaluation > semantic positivity-evaluation contrast. Patients showed greater activation mainly within the posterior cingulate gyrus (PCC) as compared to controls for the other-evaluation > semantic positivity-evaluation contrast. Furthermore, gray matter volume was reduced in the MPFC, temporal lobe, cuneus, and the dorsal lateral prefrontal cortex (DLPFC) among the patient group when compared to controls. The present study adds to previous findings regarding self- and other-referential processing in schizophrenia, providing support for neurobiological models of self-reflection impairment. PMID:26406464

Acute LSD effects on response inhibition neural networks.

PubMed

Schmidt, A; Müller, F; Lenz, C; Dolder, P C; Schmid, Y; Zanchi, D; Lang, U E; Liechti, M E; Borgwardt, S

2017-10-02

Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations. In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire. Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery. Our findings show that 5-HT2AR activation by LSD leads to a hippocampal-prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

PubMed

Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Brain hyper-connectivity and operation-specific deficits during arithmetic problem solving in children with developmental dyscalculia

PubMed Central

Rosenberg-Lee, Miriam; Ashkenazi, Sarit; Chen, Tianwen; Young, Christina B.; Geary, David C.; Menon, Vinod

2014-01-01

Developmental dyscalculia (DD) is marked by specific deficits in processing numerical and mathematical information despite normal intelligence (IQ) and reading ability. We examined how brain circuits used by young children with DD to solve simple addition and subtraction problems differ from those used by typically developing (TD) children who were matched on age, IQ, reading ability, and working memory. Children with DD were slower and less accurate during problem solving than TD children, and were especially impaired on their ability to solve subtraction problems. Children with DD showed significantly greater activity in multiple parietal, occipito-temporal and prefrontal cortex regions while solving addition and subtraction problems. Despite poorer performance during subtraction, children with DD showed greater activity in multiple intra-parietal sulcus (IPS) and superior parietal lobule subdivisions in the dorsal posterior parietal cortex as well as fusiform gyrus in the ventral occipito-temporal cortex. Critically, effective connectivity analyses revealed hyper-connectivity, rather than reduced connectivity, between the IPS and multiple brain systems including the lateral fronto-parietal and default mode networks in children with DD during both addition and subtraction. These findings suggest the IPS and its functional circuits are a major locus of dysfunction during both addition and subtraction problem solving in DD, and that inappropriate task modulation and hyper-connectivity, rather than under-engagement and under-connectivity, are the neural mechanisms underlying problem solving difficulties in children with DD. We discuss our findings in the broader context of multiple levels of analysis and performance issues inherent in neuroimaging studies of typical and atypical development. PMID:25098903

Brain hyper-connectivity and operation-specific deficits during arithmetic problem solving in children with developmental dyscalculia.

PubMed

Rosenberg-Lee, Miriam; Ashkenazi, Sarit; Chen, Tianwen; Young, Christina B; Geary, David C; Menon, Vinod

2015-05-01

Developmental dyscalculia (DD) is marked by specific deficits in processing numerical and mathematical information despite normal intelligence (IQ) and reading ability. We examined how brain circuits used by young children with DD to solve simple addition and subtraction problems differ from those used by typically developing (TD) children who were matched on age, IQ, reading ability, and working memory. Children with DD were slower and less accurate during problem solving than TD children, and were especially impaired on their ability to solve subtraction problems. Children with DD showed significantly greater activity in multiple parietal, occipito-temporal and prefrontal cortex regions while solving addition and subtraction problems. Despite poorer performance during subtraction, children with DD showed greater activity in multiple intra-parietal sulcus (IPS) and superior parietal lobule subdivisions in the dorsal posterior parietal cortex as well as fusiform gyrus in the ventral occipito-temporal cortex. Critically, effective connectivity analyses revealed hyper-connectivity, rather than reduced connectivity, between the IPS and multiple brain systems including the lateral fronto-parietal and default mode networks in children with DD during both addition and subtraction. These findings suggest the IPS and its functional circuits are a major locus of dysfunction during both addition and subtraction problem solving in DD, and that inappropriate task modulation and hyper-connectivity, rather than under-engagement and under-connectivity, are the neural mechanisms underlying problem solving difficulties in children with DD. We discuss our findings in the broader context of multiple levels of analysis and performance issues inherent in neuroimaging studies of typical and atypical development. © 2014 John Wiley & Sons Ltd.

The association between cognitive deficits and prefrontal hemodynamic responses during performance of working memory task in patients with schizophrenia.

PubMed

Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

2016-04-01

Schizophrenia-associated cognitive deficits are resistant to treatment and thus pose a lifelong burden. The Brief Assessment of Cognition in Schizophrenia (BACS) provides reliable and valid assessments across cognitive domains. However, because the prefrontal functional abnormalities specifically associated with the level of cognitive deficits in schizophrenia have not been examined, we explored this relationship. Patients with schizophrenia (N=87) and matched healthy controls (N=50) participated in the study. Using near-infrared spectroscopy (NIRS), we measured the hemodynamic responses in the prefrontal and superior temporal cortical surface areas during a working memory task. Correlation analyses revealed a relationship between the hemodynamics and the BACS composite and domain scores. Hemodynamic responses of the left dorsolateral prefrontal cortex (DLPFC) and left frontopolar cortex (FPC) in the higher-level-of-cognitive-function schizophrenia group were weaker than the responses of the controls but similar to those of the lower-level-of-cognitive-function schizophrenia group. However, hemodynamic responses in the right DLPFC, bilateral ventrolateral PFC (VLPFC), and right temporal regions decreased with increasing cognitive deficits. In addition, the hemodynamic response correlated positively with the level of cognitive function (BACS composite scores) in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions in schizophrenia. The correlation was driven by all BACS domains. Our results suggest that the linked functional deficits in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions may be related to BACS-measured cognitive impairments in schizophrenia and show that linking the neurocognitive deficits and brain abnormalities can increase our understanding of schizophrenia pathophysiology. Copyright © 2015 Elsevier B.V. All rights reserved.

Regional neuronal network failure and cognition in late-onset sporadic Alzheimer disease.

PubMed

Carter, S F; Embleton, K V; Anton-Rodriguez, J M; Burns, A; Ralph, M A L; Herholz, K

2014-06-01

The severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function. The current investigation studied the breakdown of the structure and function in regional networks involving the Papez circuit and extended neocortical association areas. Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with (18)F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls. Atrophy of the medial temporal lobes was the strongest and most consistent abnormality in patients with mild cognitive impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal regions was most strongly related to episodic memory deficits, while deficits in semantic cognition were also strongly related to reductions of glucose metabolism in the posterior cingulate cortex and temporoparietal regions. Changes in fractional anisotropy within white matter tracts, particularly in the left cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus, were significantly associated with the cognitive deficits in multiple regression analyses. Posterior cingulate and orbitofrontal metabolic deficits appeared to be related to microstructural changes in projecting white matter tracts. Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the most prominent lesion, with associated impairment of the uncinate and cingulum white matter microstructures and hippocampal and posterior cingulate metabolic impairment. © 2014 by American Journal of Neuroradiology.

Thalamocortical Connections and Executive Function in Pediatric Temporal and Frontal Lobe Epilepsy.

PubMed

Law, N; Smith, M L; Widjaja, E

2018-06-07

Largely accepted in the literature is the role the interconnections between the thalamus and cortex play in generalized epilepsy. However, thalamocortical involvement is less understood in focal epilepsy in terms of the effect of seizures on thalamocortical circuitry in the developing brain and subsequent cognitive outcome. We investigated thalamocortical pathway microstructure in pediatric frontal lobe epilepsy and temporal lobe epilepsy and examined the associations between pathway microstructure and measures of executive function. We examined thalamocortical connections in 24 children with frontal lobe epilepsy, 17 patients with temporal lobe epilepsy, and 25 healthy children using DTI. We investigated several executive function measures in patients and controls, which were distilled into latent executive function components to compare among groups, and the associations between measures of thalamocortical microstructure and executive function. We found no differences in thalamocortical pathway microstructure between the groups, but aspects of executive function (mental flexibility/inhibition/shifting) were impaired in the frontal lobe epilepsy group compared with controls. In patients with frontal lobe epilepsy, younger age at seizure onset and a greater number of antiepileptic drugs were associated with DTI indices indicative of damaged/less developed thalamocortical pathways. In patients with temporal lobe epilepsy, poorer performance on all measures of executive function was associated with DTI indices reflective of damaged/less developed pathways. Our results give insight into vulnerable neural networks in pediatric focal epilepsy and suggest thalamocortical pathway damage as a potential mechanism of executive function impairment in temporal lobe epilepsy but not frontal lobe epilepsy. Identifying structure-function relations can help inform how we measure functional and cognitive/behavioral outcomes in these populations. © 2018 by American Journal of Neuroradiology.

The topology of connections between rat prefrontal and temporal cortices

PubMed Central

Bedwell, Stacey A.; Billett, E. Ellen; Crofts, Jonathan J.; MacDonald, Danielle M.; Tinsley, Chris J.

2015-01-01

Understanding the structural organization of the prefrontal cortex (PFC) is an important step toward determining its functional organization. Here we investigated the organization of PFC using different neuronal tracers. We injected retrograde (Fluoro-Gold, 100 nl) and anterograde [Biotinylated dextran amine (BDA) or Fluoro-Ruby, 100 nl] tracers into sites within PFC subdivisions (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) along a coronal axis within PFC. At each injection site one injection was made of the anterograde tracer and one injection was made of the retrograde tracer. The projection locations of retrogradely labeled neurons and anterogradely labeled axon terminals were then analyzed in the temporal cortex: area Te, entorhinal and perirhinal cortex. We found evidence for an ordering of both the anterograde (anterior-posterior, dorsal-ventral, and medial-lateral axes: p < 0.001) and retrograde (anterior-posterior, dorsal-ventral, and medial-lateral axes: p < 0.001) connections of PFC. We observed that anterograde and retrograde labeling in ipsilateral temporal cortex (i.e., PFC inputs and outputs) often occurred reciprocally (i.e., the same brain region, such as area 35d in perirhinal cortex, contained anterograde and retrograde labeling). However, often the same specific columnar temporal cortex regions contained only either labeling of retrograde or anterograde tracer, indicating that PFC inputs and outputs are frequently non-matched. PMID:26042005

Neural correlates of episodic and semantic memory retrieval in borderline personality disorder: an fMRI study.

PubMed

Mensebach, Christoph; Beblo, Thomas; Driessen, Martin; Wingenfeld, Katja; Mertens, Markus; Rullkoetter, Nina; Lange, Wolfgang; Markowitsch, Hans J; Ollech, Isabella; Saveedra, Anamaria Silva; Rau, Harald; Woermann, Friedrich G

2009-02-28

Verbal memory impairment in borderline personality disorder (BPD) is still a matter of debate. In this study we combine investigations of both, memory retrieval as well as underlying neural circuits in BPD. Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 18 right-handed female patients with BPD and 18 matched controls during the retrieval of an episodic memory retrieval (EMR) task (free recall of a word list) and a semantic memory retrieval (SMR) task (verbal fluency). Despite unaffected performance in EMR and SMR, patients with BPD showed task-specific increased activation compared with controls. During EMR, the increased activation encompassed the posterior cingulate cortex bilaterally, the left middle and superior temporal gyrus, the right inferior frontal gyrus, and the right angular gyrus. SMR was associated with increased activation of the posterior cingulate cortex, of the right fusiform gyrus, of the left anterior cingulate cortex, and of the left postcentral gyrus. Our findings suggest that BPD patients may need to engage larger brain areas to reach a level of performance in episodic and semantic retrieval tasks that is comparable to that of healthy controls.

Transient global amnesia: implicit/explicit memory dissociation and PET assessment of brain perfusion and oxygen metabolism in the acute stage.

PubMed

Eustache, F; Desgranges, B; Petit-Taboué, M C; de la Sayette, V; Piot, V; Sablé, C; Marchal, G; Baron, J C

1997-09-01

To assess explicit memory and two components of implicit memory--that is, perceptual-verbal skill learning and lexical-semantic priming effects--as well as resting cerebral blood flow (CBF) and oxygen metabolism (CMRO2) during the acute phase of transient global amnesia. In a 59 year old woman, whose amnestic episode fulfilled all current criteria for transient global amnesia, a neuropsychological protocol was administered, including word learning, story recall, categorical fluency, mirror reading, and word stem completion tasks. PET was performed using the (15)O steady state inhalation method, while the patient still exhibited severe anterograde amnesia and was interleaved with the cognitive tests. There was a clear cut dissociation between impaired long term episodic memory and preserved implicit memory for its two components. Categorical fluency was significantly altered, suggesting word retrieval strategy--rather than semantic memory--impairment. The PET study disclosed a reduced CMRO2 with relatively or fully preserved CBF in the left prefrontotemporal cortex and lentiform nucleus, and the reverse pattern over the left occipital cortex. The PET alterations with patchy CBF-CMRO2 uncoupling would be compatible with a migraine-like phenomenon and indicate that the isolated assessment of perfusion in transient global amnesia may be misleading. The pattern of metabolic depression, with sparing of the hippocampal area, is one among the distinct patterns of brain dysfunction that underlie the (apparently) uniform clinical presentation of transient global amnesia. The finding of a left prefrontal hypometabolism in the face of impaired episodic memory and altered verbal fluency would fit present day concepts from PET activation studies about the role of this area in episodic and semantic memory encoding/retrieval. Likewise, the changes affecting the lenticular nucleus but sparing the caudate would be consistent with the normal performance in perceptual-verbal skill learning. Finally, unaltered lexical-semantic priming effects, despite left temporal cortex hypometabolism, suggest that these processes are subserved by a more distributed neocortical network.

Altered topology of neural circuits in congenital prosopagnosia.

PubMed

Rosenthal, Gideon; Tanzer, Michal; Simony, Erez; Hasson, Uri; Behrmann, Marlene; Avidan, Galia

2017-08-21

Using a novel, fMRI-based inter-subject functional correlation (ISFC) approach, which isolates stimulus-locked inter-regional correlation patterns, we compared the cortical topology of the neural circuit for face processing in participants with an impairment in face recognition, congenital prosopagnosia (CP), and matched controls. Whereas the anterior temporal lobe served as the major network hub for face processing in controls, this was not the case for the CPs. Instead, this group evinced hyper-connectivity in posterior regions of the visual cortex, mostly associated with the lateral occipital and the inferior temporal cortices. Moreover, the extent of this hyper-connectivity was correlated with the face recognition deficit. These results offer new insights into the perturbed cortical topology in CP, which may serve as the underlying neural basis of the behavioral deficits typical of this disorder. The approach adopted here has the potential to uncover altered topologies in other neurodevelopmental disorders, as well.

Medial temporal lobe structure and cognition in individuals with schizophrenia and in their non-psychotic siblings.

PubMed

Karnik-Henry, Meghana S; Wang, Lei; Barch, Deanna M; Harms, Michael P; Campanella, Carolina; Csernansky, John G

2012-07-01

Medial temporal lobe (MTL) structures play a central role in episodic memory. Prior studies suggest that individuals with schizophrenia have deficits in episodic memory as well as structural abnormalities of the medial temporal lobe (MTL). While correlations have been reported between MTL volume loss and episodic memory deficits in such individuals, it is not clear whether such correlations reflect the influence of the disease state or of underlying genetic influences that might contribute to risk. We used high resolution magnetic resonance imaging and probabilistic algorithms for image analysis to determine whether MTL structure, episodic memory performance and the relationship between the two differed among groups of 47 healthy control subjects, 50 control siblings, 39 schizophrenia subjects, and 33 siblings of schizophrenia subjects. High-dimensional large deformation brain mapping was used to obtain volume measures of the hippocampus. Cortical distance mapping was used to obtain volume and thickness measures of the parahippocampal gyrus (PHG) and its substructures: the entorhinal cortex (ERC), the perirhinal cortex (PRC), and the parahippocampal cortex (PHC). Neuropsychological data was used to establish an episodic memory domain score for each subject. Both schizophrenia subjects and their siblings displayed abnormalities in episodic memory performance. Siblings of individuals with schizophrenia, and to a lesser extent, individuals with schizophrenia themselves, displayed abnormalities in measures of MTL structure (volume loss or cortical thinning) as compared to control groups. Further, we observed correlations between structural measures and memory performance in both schizophrenia subjects and their siblings, but not in their respective control groups. These findings suggest that disease-specific genetic factors present in both patients and their relatives may be responsible for correlated abnormalities of MTL structure and memory impairment. The observed attenuated effect of such factors on MTL structure in individuals with schizophrenia may be due to non-genetic influences related to the development and progression of the disease on global brain structure and cognitive processing. Copyright © 2012 Elsevier B.V. All rights reserved.

Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system?

PubMed

Eyre, Janet A; Smith, Martin; Dabydeen, Lyvia; Clowry, Gavin J; Petacchi, Eliza; Battini, Roberta; Guzzetta, Andrea; Cioni, Giovanni

2007-11-01

Subjects with severe hemiplegic cerebral palsy have increased ipsilateral corticospinal projections from their noninfarcted cortex. We investigated whether their severe impairment might, in part, be caused by activity-dependent, competitive displacement of surviving contralateral corticospinal projections from the affected cortex by more active ipsilateral corticospinal projections from the nonaffected cortex, thereby compounding the impairment. Transcranial magnetic stimulation (TMS) characterized corticospinal tract development from each hemisphere over the first 2 years in 32 healthy children, 14 children with unilateral stroke, and 25 with bilateral lesions. Magnetic resonance imaging and anatomic studies compared corticospinal tract growth in 13 patients with perinatal stroke with 46 healthy subjects. Infants with unilateral lesions initially had responses after TMS of the affected cortex, which became progressively more abnormal, and seven were eventually lost. There was associated hypertrophy of the ipsilateral corticospinal axons projecting from the noninfarcted cortex. Magnetic resonance imaging and anatomic studies demonstrated hypertrophy of the corticospinal tract from the noninfarcted hemisphere. TMS findings soon after the stroke did not predict impairment; subsequent loss of responses and hypertrophy of ipsilateral corticospinal axons from the noninfarcted cortex predicted severe impairment at 2 years. Infants with bilateral lesions maintained responses to TMS from both hemispheres with a normal pattern of development. Rather than representing "reparative plasticity," increased ipsilateral projections from the noninfarcted cortex compound disability by competitively displacing surviving contralateral corticospinal projections from the infarcted cortex. This may provide a pathophysiological explanation for why signs of hemiplegic cerebral palsy appear late and progress over the first 2 years of life.

Technetium-99m HMPAO brain SPECT in autistic children and their families.

PubMed

Degirmenci, Berna; Miral, Süha; Kaya, Gamze Capa; Iyilikçi, Leyla; Arslan, Gulhan; Baykara, Ayşen; Evren, Ismail; Durak, Hatice

2008-04-15

The purpose of the study was to investigate perfusion patterns in autistic children (AC) and their families. Ten AC (9 boys, 1 girl; mean age: 6.9+/-1.7 years) with autistic disorder defined by DSM-III-R criteria, five age-matched children (3 boys, 2 girls) as a control group, and the immediate family members of eight AC (8 mothers, 8 fathers, 7 siblings; mean ages: 39+/-4 years, 36+/-5 years and 13+/-5 years, respectively) were included in the study. Age- and sex-matched control groups for both the parents and the siblings were also included in the study. Brain perfusion images were obtained 1 h after the intravenous injection of an adjusted dose of Tc-99m HMPAO to children and the adults. Visual and semiquantitative evaluations were performed. Hypoperfusion was seen in the right posterior parietal cortex in three AC, in bilateral parietal cortex in one AC, bilateral frontal cortex in two AC, left parietal and temporal cortex in one AC, and right parietal and temporal cortex in one AC. Asymmetric perfusion was observed in the caudate nucleus in four AC. In semiquantitative analyses, statistically significant hypoperfusion was found in the right inferior and superior frontal, left superior frontal, right parietal, right mesial temporal and right caudate nucleus. In parents of AC, significant hypoperfusion was noted in the right parietal and bilateral inferior frontal cortex. In siblings of AC, perfusion in the right frontal cortex, right nucleus caudate and left parietal cortex was significantly decreased. This preliminary study suggests the existence of regional brain perfusion alterations in frontal, temporal, and parietal cortex and in caudate nucleus in AC and in their first-degree family members.

Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex

PubMed Central

Li, Xiao; Yu, Kai; Zhang, Zicong; Sun, Wenjian; Yang, Zhou; Feng, Jingyu; Chen, Xi; Liu, Chun-Hua; Wang, Haitao; Guo, Yi Ping; He, Jufang

2014-01-01

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex. PMID:24343575

Multisensory connections of monkey auditory cerebral cortex

PubMed Central

Smiley, John F.; Falchier, Arnaud

2009-01-01

Functional studies have demonstrated multisensory responses in auditory cortex, even in the primary and early auditory association areas. The features of somatosensory and visual responses in auditory cortex suggest that they are involved in multiple processes including spatial, temporal and object-related perception. Tract tracing studies in monkeys have demonstrated several potential sources of somatosensory and visual inputs to auditory cortex. These include potential somatosensory inputs from the retroinsular (RI) and granular insula (Ig) cortical areas, and from the thalamic posterior (PO) nucleus. Potential sources of visual responses include peripheral field representations of areas V2 and prostriata, as well as the superior temporal polysensory area (STP) in the superior temporal sulcus, and the magnocellular medial geniculate thalamic nucleus (MGm). Besides these sources, there are several other thalamic, limbic and cortical association structures that have multisensory responses and may contribute cross-modal inputs to auditory cortex. These connections demonstrated by tract tracing provide a list of potential inputs, but in most cases their significance has not been confirmed by functional experiments. It is possible that the somatosensory and visual modulation of auditory cortex are each mediated by multiple extrinsic sources. PMID:19619628

Dissociating movement from movement timing in the rat primary motor cortex.

PubMed

Knudsen, Eric B; Powers, Marissa E; Moxon, Karen A

2014-11-19

Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions. Copyright © 2014 the authors 0270-6474/14/3415576-11$15.00/0.

Local cerebral glucose utilization during status epilepticus in newborn primates

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

Fujikawa, D.G.; Dwyer, B.E.; Lake, R.R.

1989-06-01

The effect of bicuculline-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) was studied in 2-wk-old ketamine-anesthetized marmoset monkeys, using the 2-(/sup 14/C)-deoxy-D-glucose autoradiographical technique. To estimate LCMRglc in cerebral cortex and thalamus during SE, the lumped constant (LC) for 2-deoxy-D-glucose (2-DG) and the rate constants for 2-DG and glucose were calculated for these regions. The control LC was 0.43 in frontoparietal cortex, 0.51 in temporal cortex, and 0.50 in thalamus; it increased to 1.07 in frontoparietal cortex, 1.13 in temporal cortex, and 1.25 in thalamus after 30 min of seizures. With control LC values, LCMRglc inmore » frontoparietal cortex, temporal cortex, and dorsomedial thalamus appeared to increase four to sixfold. With seizure LC values, LCMRglc increased 1.5- to 2-fold and only in cortex. During 45-min seizures, LCMRglc in cortex and thalamus probably increases 4- to 6-fold initially and later falls to the 1.5- to 2-fold level as tissue glucose concentrations decrease. Together with our previous results demonstrating depletion of high-energy phosphates and glucose in these regions, the data suggest that energy demands exceed glucose supply. The long-term effects of these metabolic changes on the developing brain remain to be determined.« less

Ventromedial prefrontal and anterior cingulate cortex adopt choice and default reference frames during sequential multialternative choice

PubMed Central

Boorman, Erie D; Rushworth, Matthew F; Behrens, Tim E

2013-01-01

Although damage to medial frontal cortex causes profound decision-making impairments, it has been difficult to pinpoint the relative contributions of key anatomical subdivisions. Here we use fMRI to examine the contributions of human ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC) during sequential choices between multiple alternatives – two key features of choices made in ecological settings. By carefully constructing options whose current value at any given decision was dissociable from their longer-term value, we were able to examine choices in current and long-term frames of reference. We present evidence showing that activity at choice and feedback in vmPFC and dACC was tied to the current choice and the best long-term option, respectively. vmPFC, mid-cingulate, and PCC encoded the relative value between the chosen and next-best option at each sequential decision, whereas dACC encoded the relative value of adapting choices from the option with the highest value in the longer-term. Furthermore, at feedback we identify temporally dissociable effects that predict repetition of the current choice and adaptation away from the long-term best option in vmPFC and dACC, respectively. These functional dissociations at choice and feedback suggest that sequential choices are subject to competing cortical mechanisms. PMID:23392656

Decision-making performance in Parkinson's disease correlates with lateral orbitofrontal volume.

PubMed

Kobayakawa, Mutsutaka; Tsuruya, Natsuko; Kawamura, Mitsuru

2017-01-15

Patients with Parkinson's disease (PD) exhibit poor decision-making, and the underlying neural correlates are unclear. We used voxel-based morphometry with Diffeomorphic Anatomical Registration through Exponentiated Lie algebra to examine this issue. The decision-making abilities of 20 patients with PD and 37 healthy controls (HCs) were measured with a computerized Iowa Gambling Task (IGT). We assessed the local gray matter volumes of the patients and HCs and their correlations with decision-making performance, disease duration, disease severity, and anti-Parkinsonism medication dose. Compared with the HCs, the patients with PD exhibited poor IGT performances. The gray matter volumes in the medial orbitofrontal cortex, left inferior temporal cortex, and right middle frontal gyrus were decreased in the patients. Results in the regression analysis showed that lateral orbitofrontal volume correlated with performance in the IGT in PD. Regions that correlated with disease duration, severity, and medication dose did not overlap with orbitofrontal regions. Our results indicate that the lateral and medial orbitofrontal cortex are related to decision-making in PD patients. Since the medial orbitofrontal cortex is shown to be involved in monitoring reward, reward monitoring seems to be impaired as a whole in PD patients. Meanwhile, the lateral region is related to evaluation of punishment, which is considered to have an influence on individual differences in decision-making performance in PD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

MEG Working Memory N-Back Task Reveals Functional Deficits in Combat-Related Mild Traumatic Brain Injury.

PubMed

Huang, Ming-Xiong; Nichols, Sharon; Robb-Swan, Ashley; Angeles-Quinto, Annemarie; Harrington, Deborah L; Drake, Angela; Huang, Charles W; Song, Tao; Diwakar, Mithun; Risbrough, Victoria B; Matthews, Scott; Clifford, Royce; Cheng, Chung-Kuan; Huang, Jeffrey W; Sinha, Anusha; Yurgil, Kate A; Ji, Zhengwei; Lerman, Imanuel; Lee, Roland R; Baker, Dewleen G

2018-04-13

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive impairment in military service members and Veterans. However, the mechanism of persistent cognitive deficits including working memory (WM) dysfunction is not fully understood in mTBI. Few studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in combat-related mTBI. Study participants included 25 symptomatic active-duty service members or Veterans with combat-related mTBI and 20 healthy controls with similar combat experiences. MEG source-magnitude images were obtained for alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and low-frequency (1-7 Hz) bands. Compared with healthy combat controls, mTBI participants showed increased MEG signals across frequency bands in frontal pole (FP), ventromedial prefrontal cortex, orbitofrontal cortex (OFC), and anterior dorsolateral prefrontal cortex (dlPFC), but decreased MEG signals in anterior cingulate cortex. Hyperactivations in FP, OFC, and anterior dlPFC were associated with slower reaction times. MEG activations in lateral FP also negatively correlated with performance on tests of letter sequencing, verbal fluency, and digit symbol coding. The profound hyperactivations from FP suggest that FP is particularly vulnerable to combat-related mTBI.

Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

PubMed

Martin, J H; Donarummo, L; Hacking, A

2000-02-01

This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.

Extensive cytotoxic lesions of the rat retrosplenial cortex reveal consistent deficits on tasks that tax allocentric spatial memory.

PubMed

Vann, Seralynne D; Aggleton, John P

2002-02-01

Despite the connections of the retrosplenial cortex strongly suggesting a role in spatial memory, the lesion data to date have been equivocal. Whether subjects are impaired after retrosplenial lesions seems to depend on whether the lesions were aspirative or excitotoxic, with the latter failing to produce an impairment. A shortcoming of previous excitotoxic lesion studies is that they spared the most caudal part of the retrosplenial cortex. The present study thus used rats with extensive neurotoxic lesions of the retrosplenial cortex that encompassed the entire rostrocaudal extent of this region. These rats were consistently impaired on several tests that tax allocentric memory. In contrast, they were unimpaired on an egocentric discrimination task. Although the lesions did not appear to affect object recognition, clear deficits were found for an object-in-place discrimination. The present study not only demonstrates a role for the retrosplenial cortex in allocentric spatial memory, but also explains why previous excitotoxic lesions have failed to detect any deficits.

Migratory stroke-like lesions in a case of adult-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and a review of imaging findings.

PubMed

Cai, Stephen S; von Coelln, Rainer; Kouo, Theresa J

2016-12-01

Imaging findings of adult-onset mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is poorly documented. The authors present a 48-year-old woman with subacute onset of word-finding difficulties and right arm stiffness. Magnetic resonance imaging performed 2 weeks prior revealed left temporal lobe diffusion and fluid-attenuated inversion recovery hyperintensity predominantly involving the cortex. The apparent diffusion coefficient map showed preserved signal in the temporal cortex. Subsequent magnetic resonance imagings demonstrated a new diffusion signal abnormality extending to the left parietal cortex and occipital cortex with resolving diffusion hyperintensity in the temporal lobe. MR spectroscopy showed scattered areas of lactate deposition. Diagnosis of MELAS syndrome was confirmed by genetic analysis. Fluctuating, migratory stroke-like lesions with a predilection for the parietal, temporal, and occipital cortex that do not conform to a vascular territory and a lactate spike at 1.3 ppm on MR spectroscopy are characteristic of MELAS syndrome. Preserved signal intensity on apparent diffusion coefficient is useful to distinguish MELAS syndrome from ischemic infarction where the signal is typically reduced.

Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

NASA Technical Reports Server (NTRS)

Krukowski, A. E.; Miller, K. D.

2001-01-01

Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

Gray matter network measures are associated with cognitive decline in mild cognitive impairment.

PubMed

Dicks, Ellen; Tijms, Betty M; Ten Kate, Mara; Gouw, Alida A; Benedictus, Marije R; Teunissen, Charlotte E; Barkhof, Frederik; Scheltens, Philip; van der Flier, Wiesje M

2018-01-01

Gray matter networks are disrupted in Alzheimer's disease and related to cognitive impairment. However, it is still unclear whether these disruptions are associated with cognitive decline over time. Here, we studied this question in a large sample of patients with mild cognitive impairment with extensive longitudinal neuropsychological assessments. Gray matter networks were extracted from baseline structural magnetic resonance imaging, and we tested associations of network measures and cognitive decline in Mini-Mental State Examination and 5 cognitive domains (i.e., memory, attention, executive function, visuospatial, and language). Disrupted network properties were cross-sectionally related to worse cognitive impairment. Longitudinally, lower small-world coefficient values were associated with a steeper decline in almost all domains. Lower betweenness centrality values correlated with a faster decline in Mini-Mental State Examination and memory, and at a regional level, these associations were specific for the precuneus, medial frontal, and temporal cortex. Furthermore, network measures showed additive value over established biomarkers in predicting cognitive decline. Our results suggest that gray matter network measures might have use in identifying patients who will show fast disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

TDP-43 Promotes Neurodegeneration by Impairing Chromatin Remodeling.

PubMed

Berson, Amit; Sartoris, Ashley; Nativio, Raffaella; Van Deerlin, Vivianna; Toledo, Jon B; Porta, Sílvia; Liu, Shichong; Chung, Chia-Yu; Garcia, Benjamin A; Lee, Virginia M-Y; Trojanowski, John Q; Johnson, F Brad; Berger, Shelley L; Bonini, Nancy M

2017-12-04

Regulation of chromatin structure is critical for brain development and function. However, the involvement of chromatin dynamics in neurodegeneration is less well understood. Here we find, launching from Drosophila models of amyotrophic lateral sclerosis and frontotemporal dementia, that TDP-43 impairs the induction of multiple key stress genes required to protect from disease by reducing the recruitment of the chromatin remodeler Chd1 to chromatin. Chd1 depletion robustly enhances TDP-43-mediated neurodegeneration and promotes the formation of stress granules. Conversely, upregulation of Chd1 restores nucleosomal dynamics, promotes normal induction of protective stress genes, and rescues stress sensitivity of TDP-43-expressing animals. TDP-43-mediated impairments are conserved in mammalian cells, and, importantly, the human ortholog CHD2 physically interacts with TDP-43 and is strikingly reduced in level in temporal cortex of human patient tissue. These findings indicate that TDP-43-mediated neurodegeneration causes impaired chromatin dynamics that prevents appropriate expression of protective genes through compromised function of the chromatin remodeler Chd1/CHD2. Enhancing chromatin dynamics may be a treatment approach to amyotrophic lateral scleorosis (ALS)/frontotemporal dementia (FTD). Copyright © 2017 Elsevier Ltd. All rights reserved.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

PubMed

Lazic, Stanley E; Goodman, Anna O G; Grote, Helen E; Blakemore, Colin; Morton, A Jennifer; Hannan, Anthony J; van Dellen, Anton; Barker, Roger A

2007-06-02

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

Reading affect in the face and voice: neural correlates of interpreting communicative intent in children and adolescents with autism spectrum disorders.

PubMed

Wang, A Ting; Lee, Susan S; Sigman, Marian; Dapretto, Mirella

2007-06-01

Understanding a speaker's communicative intent in everyday interactions is likely to draw on cues such as facial expression and tone of voice. Prior research has shown that individuals with autism spectrum disorders (ASD) show reduced activity in brain regions that respond selectively to the face and voice. However, there is also evidence that activity in key regions can be increased if task demands allow for explicit processing of emotion. To examine the neural circuitry underlying impairments in interpreting communicative intentions in ASD using irony comprehension as a test case, and to determine whether explicit instructions to attend to facial expression and tone of voice will elicit more normative patterns of brain activity. Eighteen boys with ASD (aged 7-17 years, full-scale IQ >70) and 18 typically developing (TD) boys underwent functional magnetic resonance imaging at the Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles. Blood oxygenation level-dependent brain activity during the presentation of short scenarios involving irony. Behavioral performance (accuracy and response time) was also recorded. Reduced activity in the medial prefrontal cortex and right superior temporal gyrus was observed in children with ASD relative to TD children during the perception of potentially ironic vs control scenarios. Importantly, a significant group x condition interaction in the medial prefrontal cortex showed that activity was modulated by explicit instructions to attend to facial expression and tone of voice only in the ASD group. Finally, medial prefrontal cortex activity was inversely related to symptom severity in children with ASD such that children with greater social impairment showed less activity in this region. Explicit instructions to attend to facial expression and tone of voice can elicit increased activity in the medial prefrontal cortex, part of a network important for understanding the intentions of others, in children with ASD. These findings suggest a strategy for future intervention research.

Different Cortical Dynamics in Face and Body Perception: An MEG study

PubMed Central

Meeren, Hanneke K. M.; de Gelder, Beatrice; Ahlfors, Seppo P.; Hämäläinen, Matti S.; Hadjikhani, Nouchine

2013-01-01

Evidence from functional neuroimaging indicates that visual perception of human faces and bodies is carried out by distributed networks of face and body-sensitive areas in the occipito-temporal cortex. However, the dynamics of activity in these areas, needed to understand their respective functional roles, are still largely unknown. We monitored brain activity with millisecond time resolution by recording magnetoencephalographic (MEG) responses while participants viewed photographs of faces, bodies, and control stimuli. The cortical activity underlying the evoked responses was estimated with anatomically-constrained noise-normalised minimum-norm estimate and statistically analysed with spatiotemporal cluster analysis. Our findings point to distinct spatiotemporal organization of the neural systems for face and body perception. Face-selective cortical currents were found at early latencies (120–200 ms) in a widespread occipito-temporal network including the ventral temporal cortex (VTC). In contrast, early body-related responses were confined to the lateral occipito-temporal cortex (LOTC). These were followed by strong sustained body-selective responses in the orbitofrontal cortex from 200–700 ms, and in the lateral temporal cortex and VTC after 500 ms latency. Our data suggest that the VTC region has a key role in the early processing of faces, but not of bodies. Instead, the LOTC, which includes the extra-striate body area (EBA), appears the dominant area for early body perception, whereas the VTC contributes to late and post-perceptual processing. PMID:24039712

The effects of anterior arcuate and dorsomedial frontal cortex lesions on visually guided eye movements: 2. Paired and multiple targets.

PubMed

Schiller, P H; Chou, I

2000-01-01

This study examined the effects of anterior arcuate and dorsomedial frontal cortex lesions on the execution of saccadic eye movements made to paired and multiple targets in rhesus monkeys. Identical paired targets were presented with various temporal asynchronies to determine the temporal offset required to yield equal probability choices to either target. In the intact animal equal probability choices were typically obtained when the targets appeared simultaneously. After unilateral anterior arcuate lesions a major shift arose in the temporal offset required to obtain equal probability choices for paired targets that necessitated presenting the target in the hemifield contralateral to the lesion more than 100 ms prior to the target in the ipsilateral hemifield. This deficit was still pronounced 1 year after the lesion. Dorsomedial frontal cortex lesions produced much smaller but significant shifts in target selection that recovered more rapidly. Paired lesions produced deficits similar to those observed with anterior arcuate lesions alone. Major deficits were also observed on a multiple target temporal discrimination task after anterior arcuate but not after dorsomedial frontal cortex lesions. These results suggest that the frontal eye fields that reside in anterior bank of the arcuate sulcus play an important role in temporal processing and in target selection. Dorsomedial frontal cortex, that contains the medial eye fields, plays a much less important role in the execution of these tasks.

Prefrontal gray matter morphology mediates the association between serum anticholinergicity and cognitive functioning in early course schizophrenia.

PubMed

Wojtalik, Jessica A; Eack, Shaun M; Pollock, Bruce G; Keshavan, Matcheri S

2012-11-30

Antipsychotic and other medications used in the treatment of schizophrenia place a burden on the cholinergic subsystems of the brain, which have been associated with increased cognitive impairment in the disorder. This study sought to examine the neurobiologic correlates of the association between serum anticholinergic activity (SAA) and cognitive impairments in early schizophrenia. Neurocognitive performance on measures of memory and executive function, structural magnetic resonance imaging (MRI) scans, and SAA assays were collected from 47 early course, stabilized outpatients with schizophrenia or schizoaffective disorder. Voxel-based morphometry analyses employing general linear models, adjusting for demographic and illness-related confounds, were used to investigate the associations between SAA, gray matter morphology, and neurocognitive impairment. SAA was related to working memory and executive function impairments. Higher SAA was significantly associated with lower gray matter density in broad regions of the frontal and medial-temporal lobes, including the dorsolateral prefrontal cortex (DLPFC), hippocampus, and striatum. Lower gray matter volume in the left DLPFC was found to significantly mediate the association between SAA and working memory impairment. Disease- and/or medication-related cholinergic dysfunction may be associated with brain volume abnormalities in early course schizophrenia, which may account for the association between SAA and cognitive dysfunction in the disorder. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Divergent regional patterns of cerebral hypoperfusion and gray matter atrophy in mild cognitive impairment patients.

PubMed

Wirth, Miranka; Pichet Binette, Alexa; Brunecker, Peter; Köbe, Theresa; Witte, A Veronica; Flöel, Agnes

2017-03-01

Reductions of cerebral blood flow and gray matter structure have been implicated in early pathogenesis of Alzheimer's disease, potentially providing complementary information. The present study evaluated regional patterns of cerebral hypoperfusion and atrophy in patients with mild cognitive impairment and healthy older adults. In each participant, cerebral perfusion and gray matter structure were extracted within selected brain regions vulnerable to Alzheimer's disease using magnetic resonance imaging. Measures were compared between diagnostic groups with/without adjustment for covariates. In mild cognitive impairment patients, cerebral blood flow was significantly reduced in comparison with healthy controls in temporo-parietal regions and the basal ganglia in the absence of local gray matter atrophy. By contrast, gray matter structure was significantly reduced in the hippocampus in the absence of local hypoperfusion. Both, cerebral perfusion and gray matter structure were significantly reduced in the entorhinal and isthmus cingulate cortex in mild cognitive impairment patients compared with healthy older adults. Our results demonstrated partly divergent patterns of temporo-parietal hypoperfusion and medial-temporal atrophy in mild cognitive impairment patients, potentially indicating biomarker sensitivity to dissociable pathological mechanisms. The findings support applicability of cerebral perfusion and gray matter structure as complementary magnetic resonance imaging-based biomarkers in early Alzheimer's disease detection, a hypothesis to be further evaluated in longitudinal studies.

Recovery-related indicators of motor network plasticity according to impairment severity after stroke.

PubMed

Lee, J; Park, E; Lee, A; Chang, W H; Kim, D-S; Kim, Y-H

2017-10-01

Brain connectivity analysis has been widely used to investigate brain plasticity and recovery-related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery-related indicators according to initial severity. We divided participants (16 males and 14 females, aged 54.2 ± 12.0 years) into groups of different severity by Fugl-Mayer Assessment score, i.e. moderate (50-84), severe (20-49) and extremely severe (<20) impairment groups. Longitudinal resting-state functional magnetic resonance imaging data were acquired at 2 weeks and 3 months after onset. The differences in network plasticity and recovery-related indicators between groups were investigated using network distance and graph measurements. As the level of impairment increased, the network balance was more disrupted. Network balance, interhemispheric connectivity and network efficiency were recovered at 3 months only in the moderate impairment group. However, this was not the case in the extremely severe impairment group. A single connection strength between the ipsilesional primary motor cortex and ventral premotor cortex was implicated in the recovery of motor function for the extremely severe impairment group. The connections of the ipsilesional primary motor cortex-ventral premotor cortex were positively associated with motor recovery as the patients were more severely impaired. Differences in plasticity and recovery-related indicators of motor networks were noted according to impairment severity. Our results may suggest meaningful implications for recovery prediction and treatment strategies in future stroke research. © 2017 EAN.

Persistent nature of alterations in cognition and neuronal circuit excitability after exposure to simulated cosmic radiation in mice.

PubMed

Parihar, Vipan K; Maroso, Mattia; Syage, Amber; Allen, Barrett D; Angulo, Maria C; Soltesz, Ivan; Limoli, Charles L

2018-07-01

Of the many perils associated with deep space travel to Mars, neurocognitive complications associated with cosmic radiation exposure are of particular concern. Despite these realizations, whether and how realistic doses of cosmic radiation cause cognitive deficits and neuronal circuitry alterations several months after exposure remains unclear. In addition, even less is known about the temporal progression of cosmic radiation-induced changes transpiring over the duration of a time period commensurate with a flight to Mars. Here we show that rodents exposed to the second most prevalent radiation type in space (i.e. helium ions) at low, realistic doses, exhibit significant hippocampal and cortical based cognitive decrements lasting 1 year after exposure. Cosmic-radiation-induced impairments in spatial, episodic and recognition memory were temporally coincident with deficits in cognitive flexibility and reduced rates of fear extinction, elevated anxiety and depression like behavior. At the circuit level, irradiation caused significant changes in the intrinsic properties (resting membrane potential, input resistance) of principal cells in the perirhinal cortex, a region of the brain implicated by our cognitive studies. Irradiation also resulted in persistent decreases in the frequency and amplitude of the spontaneous excitatory postsynaptic currents in principal cells of the perirhinal cortex, as well as a reduction in the functional connectivity between the CA1 of the hippocampus and the perirhinal cortex. Finally, increased numbers of activated microglia revealed significant elevations in neuroinflammation in the perirhinal cortex, in agreement with the persistent nature of the perturbations in key neuronal networks after cosmic radiation exposure. These data provide new insights into cosmic radiation exposure, and reveal that even sparsely ionizing particles can disrupt the neural circuitry of the brain to compromise cognitive function over surprisingly protracted post-irradiation intervals. Copyright © 2018 Elsevier Inc. All rights reserved.

Response conflict and frontocingulate dysfunction in unmedicated participants with major depression.

PubMed

Holmes, Avram J; Pizzagalli, Diego A

2008-10-01

Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral adjustments. Prior research suggests that these deficits might be due to dysfunction within frontocingulate pathways implicated in response conflict monitoring and the recruitment of cognitive control. However, the temporal unfolding of conflict monitoring impairments in MDD remains poorly understood. To address this issue, we recorded 128-channel event-related potentials while 20 unmedicated participants with MDD and 20 demographically matched, healthy controls performed a Stroop task. Compared to healthy controls, MDD subjects showed larger Stroop interference effects and reduced N2 and N450 amplitudes. Source localization analyses at the time of maximal N450 activity revealed that MDD subjects had significantly reduced dorsal anterior cingulate cortex (dACC; Brodmann area 24/32) and left dorsolateral prefrontal cortex (Brodmann area 10/46) activation to incongruent relative to congruent trials. Consistent with the heterogeneous nature of depression, follow-up analyses revealed that depressed participants with the lowest level of conflict-related dACC activation 620 ms post-stimulus were characterized by the largest Stroop interference effects (relatively increased slowing and reduced accuracy for incongruent trials). Conversely, MDD participants with relatively stronger dACC recruitment did not differ from controls in terms of interference effects. These findings suggest that for some, but not all individuals, MDD is associated with impaired performance in trials involving competition among different response options, and reduced recruitment of frontocingulate pathways implicated in conflict monitoring and cognitive control.

When a loved one feels unfamiliar: a case study on the neural basis of Capgras delusion.

PubMed

Thiel, Christiane M; Studte, Sara; Hildebrandt, Helmut; Huster, Rene; Weerda, Riklef

2014-03-01

Perception of familiar faces depends on a core system analysing visual appearance and an extended system dealing with inference of mental states and emotional responses. Damage to the core system impairs face perception as seen in prosopagnosia. In contrast, patients with Capgras delusion show intact face perception but believe that closely related persons are impostors. It has been suggested that two deficits are necessary for the delusion, an aberrant perceptual or affective experience that leads to a bizarre belief as well as an impaired ability to evaluate beliefs. Using functional magnetic resonance imaging, we compared neural activity to familiar and unfamiliar faces in a patient with Capgras delusion and an age matched control group. We provide evidence that Capgras delusion is related to dysfunctional activity in the extended face processing system. The patient, who developed the delusion for the partner after a large right prefrontal lesion sparing the ventromedial and medial orbitofrontal cortex, lacked neural activity to the partner's face in left posterior cingulate cortex and left posterior superior temporal sulcus. Further, we found impaired functional connectivity of the latter region with the left superior frontal gyrus and to a lesser extent with the right superior frontal sulcus/middle frontal gyrus. The findings of this case study suggest that the first factor in Capgras delusion may be reduced neural activity in the extended face processing system that deals with inference of mental states while the second factor may be due to a lesion in the right middle frontal gyrus. Copyright © 2013 Elsevier Ltd. All rights reserved.

Response conflict and frontocingulate dysfunction in unmedicated participants with Major Depression

PubMed Central

Holmes, Avram J.; Pizzagalli, Diego A.

2008-01-01

Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral adjustments. Prior research suggests that these deficits might be due to dysfunction within frontocingulate pathways implicated in response conflict monitoring and the recruitment of cognitive control. However, the temporal unfolding of conflict monitoring impairments in MDD remains poorly understood. To address this issue, we recorded 128-channel event-related potentials while 20 unmedicated participants with MDD and 20 demographically matched, healthy controls performed a Stroop task. Compared to healthy controls, MDD subjects showed larger Stroop interference effects and reduced N2 and N450 amplitudes. Source localization analyses at the time of maximal N450 activity revealed that MDD subjects had significantly reduced dorsal anterior cingulate cortex (dACC; Brodmann area 24/32) and left dorsolateral prefrontal cortex (Brodmann area 10/46) activation to incongruent relative to congruent trials. Consistent with the heterogeneous nature of depression, follow-up analyses revealed that depressed participants with the lowest level of conflict-related dACC activation 620 ms post-stimulus were characterized by the largest Stroop interference effects (relatively increased slowing and reduced accuracy for incongruent trials). Conversely, MDD participants with relatively stronger dACC recruitment did not differ from controls in terms of interference effects. These findings suggest that for some, but not all individuals, MDD is associated with impaired performance in trials involving competition among different response options, and reduced recruitment of frontocingulate pathways implicated in conflict monitoring and cognitive control. PMID:18577391

Too Little and Too Much: Hypoactivation and Disinhibition of Medial Prefrontal Cortex Cause Attentional Deficits

PubMed Central

McGarrity, Stephanie; Mason, Rob; Fone, Kevin C.

2014-01-01

Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis-related dopamine hyperfunction. PMID:24899715

Anatomy of the Temporal Lobe

PubMed Central

Kiernan, J. A.

2012-01-01

Only primates have temporal lobes, which are largest in man, accommodating 17% of the cerebral cortex and including areas with auditory, olfactory, vestibular, visual and linguistic functions. The hippocampal formation, on the medial side of the lobe, includes the parahippocampal gyrus, subiculum, hippocampus, dentate gyrus, and associated white matter, notably the fimbria, whose fibres continue into the fornix. The hippocampus is an inrolled gyrus that bulges into the temporal horn of the lateral ventricle. Association fibres connect all parts of the cerebral cortex with the parahippocampal gyrus and subiculum, which in turn project to the dentate gyrus. The largest efferent projection of the subiculum and hippocampus is through the fornix to the hypothalamus. The choroid fissure, alongside the fimbria, separates the temporal lobe from the optic tract, hypothalamus and midbrain. The amygdala comprises several nuclei on the medial aspect of the temporal lobe, mostly anterior the hippocampus and indenting the tip of the temporal horn. The amygdala receives input from the olfactory bulb and from association cortex for other modalities of sensation. Its major projections are to the septal area and prefrontal cortex, mediating emotional responses to sensory stimuli. The temporal lobe contains much subcortical white matter, with such named bundles as the anterior commissure, arcuate fasciculus, inferior longitudinal fasciculus and uncinate fasciculus, and Meyer's loop of the geniculocalcarine tract. This article also reviews arterial supply, venous drainage, and anatomical relations of the temporal lobe to adjacent intracranial and tympanic structures. PMID:22934160

Impaired spontaneous anthropomorphizing despite intact perception and social knowledge

PubMed Central

Heberlein, Andrea S.; Adolphs, Ralph

2004-01-01

Humans spontaneously imbue the world with social meaning: we see not only emotions and intentional behaviors in humans and other animals, but also anger in the movements of thunderstorms and willful sabotage in crashing computers. Converging evidence supports a role for the amygdala, a collection of nuclei in the temporal lobe, in processing emotionally and socially relevant information. Here, we report that a patient with bilateral amygdala damage described a film of animated shapes (normally seen as full of social content) in entirely asocial, geometric terms, despite otherwise normal visual perception. Control tasks showed that the impairment did not result from a global inability to describe social stimuli or a bias in language use, nor was a similar impairment observed in eight comparison subjects with damage to orbitofrontal cortex. This finding extends the role of the amygdala to the social attributions we make even to stimuli that are not explicitly social and, in so doing, suggests that the human capacity for anthropomorphizing draws on some of the same neural systems as do basic emotional responses. PMID:15123799

Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

PubMed

Schubring-Giese, Maximilian; Leemburg, Susan; Luft, Andreas Rüdiger; Hosp, Jonas Aurel

2016-01-01

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session.

Altered effective connectivity anchored in the posterior cingulate cortex and the medial prefrontal cortex in cognitively intact elderly APOE ε4 carriers: a preliminary study.

PubMed

Luo, Xiao; Li, Kaicheng; Jia, Y L; Zeng, Qingze; Jiaerken, Yeerfan; Qiu, Tiantian; Huang, Peiyu; Xu, Xiaojun; Shen, Zhujing; Guan, Xiaojun; Zhou, Jiong; Wang, Chao; Xu, J J; Zhang, Minming

2018-03-17

The APOE ε4 allele is associated with impaired intrinsic functional connectivity in neural networks, especially in the default mode network (DMN). However, effective connectivity (EC) reflects the direct causal effects of one brain region to another, which has rarely been investigated. Recently, Granger causality analysis (GCA) proved suitable for the study of directionality in neuronal interactions. Using GCA, we examined the differences in the EC between the anterior medial prefrontal cortex/posterior cingulate cortex (aMPFC/PCC) and the whole brain in 17 ε4 carrying and 32 non-carrying cognitively intact elderly individuals. Furthermore, correlation analyses were performed between the abnormal EC and cognition/neuropathological indices. Compared with the non-carriers, the results showed that the ε4 carriers exhibited decreased EC from the PCC to the whole brain in the middle temporal gyrus (MTG), the anterior cingulate cortex (ACC), and the precuneus (PCu). Meanwhile, the ε4 carriers demonstrated increased EC from the whole brain to the aMPFC in the inferior parietal lobe (IPL) and the postcentral gyrus (PCG). The correlation analyses suggested that the EC from the IPL/PCG to the aMPFC was related to episodic memory in non-carriers, while the decreased EC from the PCC to the ACC was associated with increased levels of t-tau in the ε4 carriers. In ε4 carriers, a negative influence can be traced from the PCC to both the anterior and posterior DMN subsystems; meanwhile, the anterior DMN subsystem receives compensatory effects from the parietal cortex. Early increases in AD-related pathologies in the PCC may act as first factors during this pathological process.

Behavioral training enhances cortical temporal processing in neonatally deafened juvenile cats

PubMed Central

Vollmer, Maike; Raggio, Marcia W.; Schreiner, Christoph E.

2011-01-01

Deaf humans implanted with a cochlear prosthesis depend largely on temporal cues for speech recognition because spectral information processing is severely impaired. Training with a cochlear prosthesis is typically required before speech perception shows improvement, suggesting that relevant experience modifies temporal processing in the central auditory system. We tested this hypothesis in neonatally deafened cats by comparing temporal processing in the primary auditory cortex (AI) of cats that received only chronic passive intracochlear electric stimulation (ICES) with cats that were also trained with ICES to detect temporally challenging trains of electric pulses. After months of chronic passive stimulation and several weeks of detection training in behaviorally trained cats, multineuronal AI responses evoked by temporally modulated ICES were recorded in anesthetized animals. The stimulus repetition rates that produced the maximum number of phase-locked spikes (best repetition rate) and 50% cutoff rate were significantly higher in behaviorally trained cats than the corresponding rates in cats that received only chronic passive ICES. Behavioral training restored neuronal temporal following ability to levels comparable with those recorded in naïve prior normal-hearing adult deafened animals. Importantly, best repetitition rates and cutoff rates were highest for neuronal clusters activated by the electrode configuration used in behavioral training. These results suggest that neuroplasticity in the AI is induced by behavioral training and perceptual learning in animals deprived of ordinary auditory experience during development and indicate that behavioral training can ameliorate or restore temporal processing in the AI of profoundly deaf animals. PMID:21543753

Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities.

PubMed

Van Rheenen, Tamsyn E; Cropley, Vanessa; Zalesky, Andrew; Bousman, Chad; Wells, Ruth; Bruggemann, Jason; Sundram, Suresh; Weinberg, Danielle; Lenroot, Roshel K; Pereira, Avril; Shannon Weickert, Cynthia; Weickert, Thomas W; Pantelis, Christos

2018-04-06

Progress toward understanding brain mechanisms in psychosis is hampered by failures to account for within-group heterogeneity that exists across neuropsychological domains. We recently identified distinct cognitive subgroups that might assist in identifying more biologically meaningful subtypes of psychosis. In the present study, we examined whether underlying structural brain abnormalities differentiate these cognitively derived subgroups. 1.5T T1 weighted structural scans were acquired for 168 healthy controls and 220 patients with schizophrenia/schizoaffective disorder. Based on previous work, 47 patients were categorized as being cognitively compromised (impaired premorbid and current IQ), 100 as cognitively deteriorated (normal premorbid IQ, impaired current IQ), and 73 as putatively cognitively preserved (premorbid and current IQ within 1 SD of controls). Global, subcortical and cortical volume, thickness, and surface area measures were compared among groups. Whole cortex, subcortical, and regional volume and thickness reductions were evident in all subgroups compared to controls, with the largest effect sizes in the compromised group. This subgroup also showed abnormalities in regions not seen in the other patient groups, including smaller left superior and middle frontal areas, left anterior and inferior temporal areas and right lateral medial and inferior frontal, occipital lobe and superior temporal areas. This pattern of more prominent brain structural abnormalities in the group with the most marked cognitive impairments-both currently and putatively prior to illness onset, is consistent with the concept of schizophrenia as a progressive neurodevelopmental disorder. In this group, neurodevelopmental and neurodegenerative factors may be important for cognitive function.

Impaired thalamocortical connectivity in autism spectrum disorder: a study of functional and anatomical connectivity.

PubMed

Nair, Aarti; Treiber, Jeffrey M; Shukla, Dinesh K; Shih, Patricia; Müller, Ralph-Axel

2013-06-01

The thalamus plays crucial roles in the development and mature functioning of numerous sensorimotor, cognitive and attentional circuits. Currently limited evidence suggests that autism spectrum disorder may be associated with thalamic abnormalities, potentially related to sociocommunicative and other impairments in this disorder. We used functional connectivity magnetic resonance imaging and diffusion tensor imaging probabilistic tractography to study the functional and anatomical integrity of thalamo-cortical connectivity in children and adolescents with autism spectrum disorder and matched typically developing children. For connectivity with five cortical seeds (prefontal, parieto-occipital, motor, somatosensory and temporal), we found evidence of both anatomical and functional underconnectivity. The only exception was functional connectivity with the temporal lobe, which was increased in the autism spectrum disorders group, especially in the right hemisphere. However, this effect was robust only in partial correlation analyses (partialling out time series from other cortical seeds), whereas findings from total correlation analyses suggest that temporo-thalamic overconnectivity in the autism group was only relative to the underconnectivity found for other cortical seeds. We also found evidence of microstructural compromise within the thalamic motor parcel, associated with compromise in tracts between thalamus and motor cortex, suggesting that the thalamus may play a role in motor abnormalities reported in previous autism studies. More generally, a number of correlations of diffusion tensor imaging and functional connectivity magnetic resonance imaging measures with diagnostic and neuropsychological scores indicate involvement of abnormal thalamocortical connectivity in sociocommunicative and cognitive impairments in autism spectrum disorder.

Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis.

PubMed

Flore, Gemma; Di Ruberto, Giuseppina; Parisot, Joséphine; Sannino, Sara; Russo, Fabio; Illingworth, Elizabeth A; Studer, Michèle; De Leonibus, Elvira

2017-02-01

The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of COUP-TFI mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Susceptibility of Primary Sensory Cortex to Spreading Depolarizations.

PubMed

Bogdanov, Volodymyr B; Middleton, Natalie A; Theriot, Jeremy J; Parker, Patrick D; Abdullah, Osama M; Ju, Y Sungtaek; Hartings, Jed A; Brennan, K C

2016-04-27

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury. Spreading depolarizations (SDs) are involved in neurologic disorders as diverse as migraine and traumatic brain injury. In migraine, the nature of aura symptoms suggests that sensory cortex may be preferentially susceptible. In brain injury, SDs occur at a vulnerable time, during which the issue of sensory stimulation is much debated. We show, in mouse and human, that sensory cortex is more susceptible to SDs. We find that sensory stimulation biases the timing but not the location of the depolarizations. Finally, we show a relative impairment of potassium clearance in sensory cortex, providing a potential mechanism for the susceptibility. Our data help to explain the sensory nature of the migraine aura and reveal that sensory cortices are vulnerable in brain injury. Copyright © 2016 the authors 0270-6474/16/364733-11$15.00/0.

Susceptibility of Primary Sensory Cortex to Spreading Depolarizations

PubMed Central

Bogdanov, Volodymyr B.; Middleton, Natalie A.; Theriot, Jeremy J.; Parker, Patrick D.; Abdullah, Osama M.; Ju, Y. Sungtaek; Hartings, Jed A.

2016-01-01

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury. SIGNIFICANCE STATEMENT Spreading depolarizations (SDs) are involved in neurologic disorders as diverse as migraine and traumatic brain injury. In migraine, the nature of aura symptoms suggests that sensory cortex may be preferentially susceptible. In brain injury, SDs occur at a vulnerable time, during which the issue of sensory stimulation is much debated. We show, in mouse and human, that sensory cortex is more susceptible to SDs. We find that sensory stimulation biases the timing but not the location of the depolarizations. Finally, we show a relative impairment of potassium clearance in sensory cortex, providing a potential mechanism for the susceptibility. Our data help to explain the sensory nature of the migraine aura and reveal that sensory cortices are vulnerable in brain injury. PMID:27122032

Contralateral disconnection of the rat prelimbic cortex and dorsomedial striatum impairs cue-guided behavioral switching

PubMed Central

Baker, Phillip M.

2014-01-01

Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for conditional discrimination performance in which a switch in reward-predictive cues occurs every three to six trials. The GABA agonists baclofen and muscimol infused into the prelimbic cortex significantly impaired performance leading rats to adopt an inappropriate turn strategy. The NMDA receptor antagonist D-AP5 infused into the dorsomedial striatum or prelimbic cortex and dorsomedial striatum contralateral disconnection impaired performance due to a rat failing to switch a response choice for an entire trial block in about two out of 13 test blocks. In an additional study, contralateral disconnection did not affect nonswitch discrimination performance. The results suggest that the prelimbic cortex and dorsomedial striatum are necessary to support cue-guided behavioral switching. The prelimbic cortex may be critical for generating alternative response patterns while the dorsomedial striatum supports the selection of an appropriate response when cue information must be used to flexibly switch response patterns. PMID:25028395

The right parietal cortex and time perception: back to Critchley and the Zeitraffer phenomenon.

PubMed

Alexander, Iona; Cowey, Alan; Walsh, Vincent

2005-05-01

We investigated the involvement of the posterior parietal cortex in time perception by temporarily disrupting normal functioning in this region, in subjects making prospective judgements of time or pitch. Disruption of the right posterior parietal cortex significantly slowed reaction times when making time, but not pitch, judgements. Similar interference with the left parietal cortex and control stimulation over the vertex did not significantly change performance on either pitch or time tasks. The results show that the information processing necessary for temporal judgements involves the parietal cortex, probably to optimise spatiotemporal accuracy in voluntary action. The results are in agreement with a recent neuroimaging study and are discussed with regard to a psychological model of temporal processing and a recent proposal that time is part of a parietal cortex system for encoding magnitude information relevant for action.

Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception

PubMed Central

Jones, Christina B.; Lulic, Tea; Bailey, Aaron Z.; Mackenzie, Tanner N.; Mi, Yi Qun; Tommerdahl, Mark

2016-01-01

Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively. PMID:26984422

Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

PubMed

Jones, Christina B; Lulic, Tea; Bailey, Aaron Z; Mackenzie, Tanner N; Mi, Yi Qun; Tommerdahl, Mark; Nelson, Aimee J

2016-05-01

Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively. Copyright © 2016 the American Physiological Society.

Gray matter trophism, cognitive impairment, and depression in patients with multiple sclerosis.

PubMed

Pravatà, Emanuele; Rocca, Maria A; Valsasina, Paola; Riccitelli, Gianna C; Gobbi, Claudio; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

2017-12-01

Cognitive impairment and depression frequently affects patients with multiple sclerosis (MS). However, the relationship between the occurrence of depression and cognitive impairment and the development of cortical atrophy has not been fully elucidated yet. To investigate the association of cortical and deep gray matter (GM) volume with depression and cognitive impairment in MS. Three-dimensional (3D) T1-weighted scans were obtained from 126 MS patients and 59 matched healthy controls. Cognitive impairment was assessed using the Brief Repeatable Battery of Neuropsychological Tests and depression with the Montgomery-Asberg Depression Rating Scale (MADRS). Using FreeSurfer and FIRST software, we assessed cortical thickness (CTh) and deep GM volumetry. Magnetic resonance imaging (MRI) variables explaining depression and cognitive impairment were investigated using factorial and classification analysis. Multivariate regression models correlated GM abnormalities with symptoms severity. Compared with controls, MS patients exhibited widespread bilateral cortical thinning involving all brain lobes. Depressed MS showed selective CTh decrease in fronto-temporal regions, whereas cognitive impairment MS exhibited widespread fronto-parietal cortical and subcortical GM atrophy. Frontal cortical thinning was the best predictor of depression ( C-statistic = 0.7), whereas thinning of the right precuneus and high T2 lesion volume best predicted cognitive impairment ( C-statistic = 0.8). MADRS severity correlated with right entorhinal cortex thinning, whereas cognitive impairment severity correlated with left entorhinal and thalamus atrophy. MS-related depression is linked to circumscribed CTh changes in areas deputed to emotional behavior, whereas cognitive impairment is correlated with cortical and subcortical GM atrophy of circuits involved in cognition.

Early cortical metabolic rearrangement related to clinical data in idiopathic sudden sensorineural hearing loss.

PubMed

Micarelli, Alessandro; Chiaravalloti, Agostino; Viziano, Andrea; Danieli, Roberta; Schillaci, Orazio; Alessandrini, Marco

2017-07-01

Results in studies concerning cortical changes in idiopathic sudden sensorineural hearing loss (ISSNHL) are not homogeneous, in particular due to the different neuroimaging techniques implemented and the diverse stages of ISSNHL studied. Considering the recent advances in state-of-the-art positron emission tomography (PET) cameras, the aim of this study was to gain more insight into the neuroanatomical differences associated with the earliest stages of unilateral ISSNHL and clinical-perceptual performance changes. After an audiological examination including the mean auditory threshold (mean AT), mean speech discrimination score (mean SDS) and Tinnitus Handicap Inventory (THI), 14 right-handed ISSNHL patients underwent brain [ 18 F]fluorodeoxyglucose (FDG)-PET within 72 h of the onset of symptoms. When compared to an homogeneous group of 35 healthy subjects by means of statistical parametric mapping, a relative increase in FDG uptake was found in the right superior and medial frontal gyrus as well as in the right anterior cingulate cortex in ISSNHL patients. Conversely, the same group showed a significant relative decrease in FDG uptake in the right middle temporal, precentral and postcentral gyrus as well as in the left posterior cingulate cortex, left lingual, superior, middle temporal and middle frontal gyrus and in the left insula. Regression analysis showed a positive correlation between mean THI and glucose consumption in the right anterior cingulate cortex and a positive correlation between mean SDS and glucose consumption in the left precentral gyrus. The relative changes in FDG uptake found in these brain regions and the positive correlation with mean SDS and THI scores in ISSNHL could possibly highlight new aspects of cerebral rearrangement, contributing to further explain changes in those functions that support speech recognition during the sudden impairment of unilateral auditory input. Copyright © 2017 Elsevier B.V. All rights reserved.

Spatio-Temporal Patterning in Primary Motor Cortex at Movement Onset.

PubMed

Best, Matthew D; Suminski, Aaron J; Takahashi, Kazutaka; Brown, Kevin A; Hatsopoulos, Nicholas G

2017-02-01

Voluntary movement initiation involves the engagement of large populations of motor cortical neurons around movement onset. Despite knowledge of the temporal dynamics that lead to movement, the spatial structure of these dynamics across the cortical surface remains unknown. In data from 4 rhesus macaques, we show that the timing of attenuation of beta frequency local field potential oscillations, a correlate of locally activated cortex, forms a spatial gradient across primary motor cortex (MI). We show that these spatio-temporal dynamics are recapitulated in the engagement order of ensembles of MI neurons. We demonstrate that these patterns are unique to movement onset and suggest that movement initiation requires a precise spatio-temporal sequential activation of neurons in MI. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Encoding of contextual fear memory requires de novo proteins in the prelimbic cortex

PubMed Central

Rizzo, Valerio; Touzani, Khalid; Raveendra, Bindu L.; Swarnkar, Supriya; Lora, Joan; Kadakkuzha, Beena M.; Liu, Xin-An; Zhang, Chao; Betel, Doron; Stackman, Robert W.; Puthanveettil, Sathyanarayanan V.

2016-01-01

Background Despite our understanding of the significance of the prefrontal cortex in the consolidation of long-term memories (LTM), its role in the encoding of LTM remains elusive. Here we investigated the role of new protein synthesis in the mouse medial prefrontal cortex (mPFC) in encoding contextual fear memory. Methods Because a change in the association of mRNAs to polyribosomes is an indicator of new protein synthesis, we assessed the changes in polyribosome-associated mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential gene expression in mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in mPFC was determined by focal inhibition of protein synthesis (n = 131) and by intra-prelimbic cortex manipulation (n = 56) of Homer 3, a candidate identified from polyribosome profiling. Results We identified several mRNAs that are differentially and temporally recruited to polyribosomes in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL), but not in the anterior cingulate cortex (ACC) region of the mPFC immediately after CFC disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein synthesis in the PL 6 hours after CFC did not impair encoding. Furthermore, expression of Homer 3, an mRNA enriched in polyribosomes following CFC, in the PL constrained encoding of contextual fear memory. Conclusions Our studies identify several molecular substrates of new protein synthesis in the mPFC and establish that encoding of contextual fear memories require new protein synthesis in PL subregion of mPFC. PMID:28503670

Muscarinic Receptor-Dependent Long Term Depression in the Perirhinal Cortex and Recognition Memory are Impaired in the rTg4510 Mouse Model of Tauopathy.

PubMed

Scullion, Sarah E; Barker, Gareth R I; Warburton, E Clea; Randall, Andrew D; Brown, Jonathan T

2018-02-26

Neurodegenerative diseases affecting cognitive dysfunction, such as Alzheimer's disease and fronto-temporal dementia, are often associated impairments in the visual recognition memory system. Recent evidence suggests that synaptic plasticity, in particular long term depression (LTD), in the perirhinal cortex (PRh) is a critical cellular mechanism underlying recognition memory. In this study, we have examined novel object recognition and PRh LTD in rTg4510 mice, which transgenically overexpress tau P301L . We found that 8-9 month old rTg4510 mice had significant deficits in long- but not short-term novel object recognition memory. Furthermore, we also established that PRh slices prepared from rTg4510 mice, unlike those prepared from wildtype littermates, could not support a muscarinic acetylcholine receptor-dependent form of LTD, induced by a 5 Hz stimulation protocol. In contrast, bath application of the muscarinic agonist carbachol induced a form of chemical LTD in both WT and rTg4510 slices. Finally, when rTg4510 slices were preincubated with the acetylcholinesterase inhibitor donepezil, the 5 Hz stimulation protocol was capable of inducing significant levels of LTD. These data suggest that dysfunctional cholinergic innervation of the PRh of rTg4510 mice, results in deficits in synaptic LTD which may contribute to aberrant recognition memory in this rodent model of tauopathy.

Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study.

PubMed

Chiapponi, Chiara; Piras, Fabrizio; Piras, Federica; Fagioli, Sabrina; Caltagirone, Carlo; Spalletta, Gianfranco

2013-01-01

It is still unknown whether the structural brain impairments that characterize schizophrenia (SZ) worsen during the lifetime. Here, we aimed to describe age-related microstructural brain changes in cortical grey matter and subcortical white matter of patients affected by SZ. In this diffusion tensor imaging study, we included 69 patients diagnosed with SZ and 69 healthy control (HC) subjects, age and gender matched. We carried out analyses of covariance, with diagnosis as fixed factor and brain diffusion-related parameters as dependent variables, and controlled for the effect of education. White matter fractional anisotropy decreased in the entire age range spanned (18-65 years) in both SZ and HC and was significantly lower in younger patients with SZ, with no interaction (age by diagnosis) effect in fiber tracts including corpus callosum, corona radiata, thalamic radiations and external capsule. Also, grey matter mean diffusivity increased in the entire age range in both SZ and HC and was significantly higher in younger patients, with no age by diagnosis interaction in the left frontal operculum cortex, left insula and left planum polare and in the right temporal pole and right intracalcarine cortex. In individuals with SZ we found that localized brain cortical and white matter subcortical microstructural impairments appear early in life but do not worsen in the 18-65 year age range.

Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex

PubMed Central

Gilmartin, Marieke R.; Helmstetter, Fred J.

2010-01-01

The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a conditional stimulus (CS) and an aversive unconditional stimulus (UCS) across a temporal gap. In both rat and human subjects, frontal regions show increased activity during the trace interval separating the CS and UCS. We investigated the contribution of prefrontal neural activity in the rat to the acquisition of trace fear conditioning using microinfusions of the γ-aminobutyric acid type A (GABAA) receptor agonist muscimol. We also investigated the role of prefrontal N-methyl-d-aspartate (NMDA) receptor-mediated signaling in trace fear conditioning using the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Temporary inactivation of prefrontal activity with muscimol or blockade of NMDA receptor-dependent transmission in mPFC impaired the acquisition of trace, but not delay, conditional fear responses. Simultaneously acquired contextual fear responses were also impaired in drug-treated rats exposed to trace or delay, but not unpaired, training protocols. Our results support the idea that synaptic plasticity within the mPFC is critical for the long-term storage of memory in trace fear conditioning. PMID:20504949

Neural responses to affective and cognitive theory of mind in children and adolescents with autism spectrum disorder.

PubMed

Kim, Eunjoo; Kyeong, Sunghyon; Cheon, Keun-Ah; Park, Bumhee; Oh, Maeng-Keun; Chun, Ji Won; Park, Hae-Jeong; Kim, Jae-Jin; Song, Dong-Ho

2016-05-16

Children and adolescents with Autism Spectrum Disorder (ASD) are characterized by an impaired Theory of Mind (ToM). Recent evidence suggested that two aspects of ToM (cognitive ToM versus affective ToM) are differentially impaired in individuals with ASD. In this study, we examined the neural correlates of cognitive and affective ToM in children and adolescents with ASD compared to typically developing children (TDCs). Twelve children and adolescents with ASD and 12 age, IQ matched TDCs participated in this functional MRI study. The ToM task involved the attribution of cognitive and affective mental states to a cartoon character based on verbal and eye-gaze cues. In cognitive ToM tasks, ASD participants recruited the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and superior temporal gyrus (STG) to a greater extent than did TDCs. In affective ToM tasks, both ASD and TDC participants showed more activation in the insula and other subcortical regions than in cognitive ToM tasks. Correlational analysis revealed that greater activation of the mPFC/ACC regions was associated with less symptom severity in ASD patients. In sum, our study suggests that the recruitment of additional prefrontal resources can compensate for the successful behavioral performance in the ToM task in ASD participants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dissociable performance on scene learning and strategy implementation after lesions to magnocellular mediodorsal thalamic nucleus

PubMed Central

Mitchell, Anna S.; Baxter, Mark G.; Gaffan, David

2008-01-01

Monkeys with aspiration lesions of the magnocellular division of the mediodorsal thalamus (MDmc) are impaired in object-in-place scene learning, object recognition and stimulus-reward association. These data have been interpreted to mean that projections from MDmc to prefrontal cortex are required to sustain normal prefrontal function in a variety of task settings. In the present study, we investigated the extent to which bilateral neurotoxic lesions of the MDmc impair a pre-operatively learnt strategy implementation task that is impaired by a crossed lesion technique that disconnects the frontal cortex in one hemisphere from the contralateral inferotemporal cortex. Postoperative memory impairments were also examined using the object-in-place scene memory task. Monkeys learnt both strategy implementation and scene memory tasks separately to a stable level pre-operatively. Bilateral neurotoxic lesions of the MDmc, produced by 10 × 1 μl injections of a mixture of ibotenate and N-methyl-D-aspartate did not affect performance in the strategy implementation task. However, new learning of object-in-place scene memory was substantially impaired. These results provide new evidence about the role of the magnocellular mediodorsal thalamic nucleus in memory processing, indicating that interconnections with the prefrontal cortex are essential during new learning but are not required when implementing a preoperatively acquired strategy task. Thus not all functions of the prefrontal cortex require MDmc input. Instead the involvement of MDmc in prefrontal function may be limited to situations in which new learning must occur. PMID:17978029

Masking reduces orientation selectivity in rat visual cortex

PubMed Central

Alwis, Dasuni S.; Richards, Katrina L.

2016-01-01

In visual masking the perception of a target stimulus is impaired by a preceding (forward) or succeeding (backward) mask stimulus. The illusion is of interest because it allows uncoupling of the physical stimulus, its neuronal representation, and its perception. To understand the neuronal correlates of masking, we examined how masks affected the neuronal responses to oriented target stimuli in the primary visual cortex (V1) of anesthetized rats (n = 37). Target stimuli were circular gratings with 12 orientations; mask stimuli were plaids created as a binarized sum of all possible target orientations. Spatially, masks were presented either overlapping or surrounding the target. Temporally, targets and masks were presented for 33 ms, but the stimulus onset asynchrony (SOA) of their relative appearance was varied. For the first time, we examine how spatially overlapping and center-surround masking affect orientation discriminability (rather than visibility) in V1. Regardless of the spatial or temporal arrangement of stimuli, the greatest reductions in firing rate and orientation selectivity occurred for the shortest SOAs. Interestingly, analyses conducted separately for transient and sustained target response components showed that changes in orientation selectivity do not always coincide with changes in firing rate. Given the near-instantaneous reductions observed in orientation selectivity even when target and mask do not spatially overlap, we suggest that monotonic visual masking is explained by a combination of neural integration and lateral inhibition. PMID:27535373

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

Distributed Processing and Cortical Specialization for Speech and Environmental Sounds in Human Temporal Cortex

ERIC Educational Resources Information Center

Leech, Robert; Saygin, Ayse Pinar

2011-01-01

Using functional MRI, we investigated whether auditory processing of both speech and meaningful non-linguistic environmental sounds in superior and middle temporal cortex relies on a complex and spatially distributed neural system. We found that evidence for spatially distributed processing of speech and environmental sounds in a substantial…

The Consolidation of Object and Context Recognition Memory Involve Different Regions of the Temporal Lobe

ERIC Educational Resources Information Center

Balderas, Israela; Rodriguez-Ortiz, Carlos J.; Salgado-Tonda, Paloma; Chavez-Hurtado, Julio; McGaugh, James L.; Bermudez-Rattoni, Federico

2008-01-01

These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory…

Family History of Alzheimer's Disease is Associated with Impaired Perceptual Discrimination of Novel Objects.

PubMed

Mason, Emily J; Hussey, Erin P; Molitor, Robert J; Ko, Philip C; Donahue, Manus J; Ally, Brandon A

2017-01-01

Early detection may be the key to developing therapies that will combat Alzheimer's disease (AD). It has been consistently demonstrated that one of the main pathologies of AD, tau, is present in the brain decades before a clinical diagnosis. Tau pathology follows a stereotypical route through the medial temporal lobe beginning in the entorhinal and perirhinal cortices. If early pathology leads to very subtle changes in behavior, it may be possible to detect these changes in subjects years before a clinical diagnosis can currently be made. We aimed to discover if cognitively normal middle-aged adults (40-60 years old) at increased risk for AD due to family history would have impaired performance on a cognitive task known to challenge the perirhinal cortex. Using an oddity detection task, we found that subjects with a family history of AD had lowered accuracy without demonstrating differences in rate of acquisition. There were no differences between subjects' medial temporal lobe volume or cortical thickness, indicating that the changes in behavior were not due to significant atrophy. These results demonstrate that subtle changes in perceptual processing are detectable years before a typical diagnosis even when there are no differences detectable in structural imaging data. Anatomically-targeted cognitive testing may be useful in identifying subjects in the earliest stages of AD.

Encoding changes in orbitofrontal cortex in reversal-impaired aged rats.

PubMed

Schoenbaum, Geoffrey; Setlow, Barry; Saddoris, Michael P; Gallagher, Michela

2006-03-01

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.

Passive stimulation and behavioral training differentially transform temporal processing in the inferior colliculus and primary auditory cortex

PubMed Central

Beitel, Ralph E.; Schreiner, Christoph E.; Leake, Patricia A.

2016-01-01

In profoundly deaf cats, behavioral training with intracochlear electric stimulation (ICES) can improve temporal processing in the primary auditory cortex (AI). To investigate whether similar effects are manifest in the auditory midbrain, ICES was initiated in neonatally deafened cats either during development after short durations of deafness (8 wk of age) or in adulthood after long durations of deafness (≥3.5 yr). All of these animals received behaviorally meaningless, “passive” ICES. Some animals also received behavioral training with ICES. Two long-deaf cats received no ICES prior to acute electrophysiological recording. After several months of passive ICES and behavioral training, animals were anesthetized, and neuronal responses to pulse trains of increasing rates were recorded in the central (ICC) and external (ICX) nuclei of the inferior colliculus. Neuronal temporal response patterns (repetition rate coding, minimum latencies, response precision) were compared with results from recordings made in the AI of the same animals (Beitel RE, Vollmer M, Raggio MW, Schreiner CE. J Neurophysiol 106: 944–959, 2011; Vollmer M, Beitel RE. J Neurophysiol 106: 2423–2436, 2011). Passive ICES in long-deaf cats remediated severely degraded temporal processing in the ICC and had no effects in the ICX. In contrast to observations in the AI, behaviorally relevant ICES had no effects on temporal processing in the ICC or ICX, with the single exception of shorter latencies in the ICC in short-deaf cats. The results suggest that independent of deafness duration passive stimulation and behavioral training differentially transform temporal processing in auditory midbrain and cortex, and primary auditory cortex emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf cat. NEW & NOTEWORTHY Behaviorally relevant vs. passive electric stimulation of the auditory nerve differentially affects neuronal temporal processing in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (AI) in profoundly short-deaf and long-deaf cats. Temporal plasticity in the ICC depends on a critical amount of electric stimulation, independent of its behavioral relevance. In contrast, the AI emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf auditory system. PMID:27733594

Acute cortical deafness in a child with MELAS syndrome.

PubMed

Pittet, Marie P; Idan, Roni B; Kern, Ilse; Guinand, Nils; Van, Hélène Cao; Toso, Seema; Fluss, Joël

2016-05-01

Auditory impairment in mitochondrial disorders are usually due to peripheral sensorineural dysfunction. Central deafness is only rarely reported. We report here an 11-year-old boy with MELAS syndrome who presented with subacute deafness after waking up from sleep. Peripheral hearing loss was rapidly excluded. A brain MRI documented bilateral stroke-like lesions predominantly affecting the superior temporal lobe, including the primary auditory cortex, confirming the central nature of deafness. Slow recovery was observed in the following weeks. This case serves to illustrate the numerous challenges caused by MELAS and the unusual occurrence of acute cortical deafness, that to our knowledge has not be described so far in a child in this setting.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

PubMed

Martínez-Levy, G A; Rocha, L; Rodríguez-Pineda, F; Alonso-Vanegas, M A; Nani, A; Buentello-García, R M; Briones-Velasco, M; San-Juan, D; Cienfuegos, J; Cruz-Fuentes, C S

2018-05-01

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Cortical thickness and surface area in neonates at high risk for schizophrenia.

PubMed

Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Ahn, Mihye; Peng, Ziwen; Zhu, Hongtu; Lin, Weili; Gilmore, John H; Shen, Dinggang

2016-01-01

Schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal pole, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal pole, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly smaller cortical surface area in the right pars triangularis (before FDR correction), compared with control neonates. This preliminary study provides the first evidence that early development of cortical thickness and surface area might be abnormal in the neonates at genetic risk for schizophrenia.

Temporal pattern of acoustic imaging noise asymmetrically modulates activation in the auditory cortex.

PubMed

Ranaweera, Ruwan D; Kwon, Minseok; Hu, Shuowen; Tamer, Gregory G; Luh, Wen-Ming; Talavage, Thomas M

2016-01-01

This study investigated the hemisphere-specific effects of the temporal pattern of imaging related acoustic noise on auditory cortex activation. Hemodynamic responses (HDRs) to five temporal patterns of imaging noise corresponding to noise generated by unique combinations of imaging volume and effective repetition time (TR), were obtained using a stroboscopic event-related paradigm with extra-long (≥27.5 s) TR to minimize inter-acquisition effects. In addition to confirmation that fMRI responses in auditory cortex do not behave in a linear manner, temporal patterns of imaging noise were found to modulate both the shape and spatial extent of hemodynamic responses, with classically non-auditory areas exhibiting responses to longer duration noise conditions. Hemispheric analysis revealed the right primary auditory cortex to be more sensitive than the left to the presence of imaging related acoustic noise. Right primary auditory cortex responses were significantly larger during all the conditions. This asymmetry of response to imaging related acoustic noise could lead to different baseline activation levels during acquisition schemes using short TR, inducing an observed asymmetry in the responses to an intended acoustic stimulus through limitations of dynamic range, rather than due to differences in neuronal processing of the stimulus. These results emphasize the importance of accounting for the temporal pattern of the acoustic noise when comparing findings across different fMRI studies, especially those involving acoustic stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Contributions of primate prefrontal cortex and medial temporal lobe to temporal-order memory.

PubMed

Naya, Yuji; Chen, He; Yang, Cen; Suzuki, Wendy A

2017-12-19

Neuropsychological and neurophysiological studies have emphasized the role of the prefrontal cortex (PFC) in maintaining information about the temporal order of events or items for upcoming actions. However, the medial temporal lobe (MTL) has also been considered critical to bind individual events or items to their temporal context in episodic memory. Here we characterize the contributions of these brain areas by comparing single-unit activity in the dorsal and ventral regions of macaque lateral PFC (d-PFC and v-PFC) with activity in MTL areas including the hippocampus (HPC), entorhinal cortex, and perirhinal cortex (PRC) as well as in area TE during the encoding phase of a temporal-order memory task. The v-PFC cells signaled specific items at particular time periods of the task. By contrast, MTL cortical cells signaled specific items across multiple time periods and discriminated the items between time periods by modulating their firing rates. Analysis of the temporal dynamics of these signals showed that the conjunctive signal of item and temporal-order information in PRC developed earlier than that seen in v-PFC. During the delay interval between the two cue stimuli, while v-PFC provided prominent stimulus-selective delay activity, MTL areas did not. Both regions of PFC and HPC exhibited an incremental timing signal that appeared to represent the continuous passage of time during the encoding phase. However, the incremental timing signal in HPC was more prominent than that observed in PFC. These results suggest that PFC and MTL contribute to the encoding of the integration of item and timing information in distinct ways.

Effects of neonatal medial versus lateral temporal cortex injury: theoretical comment on Malkova et al. (2010).

PubMed

Kolb, Bryan

2010-12-01

The article by Malkova, Mishkin, Suomo, and Bachevalier (2010, this issue) adds an important piece to our understanding of the role of the medial versus lateral temporal regions in socioemotional behavior. In their paper, they evaluate the effect of infant and adult amygdala lesions and infant inferotemporal cortex lesions on the social interactions of monkeys in infancy and adulthood. The results show that medial temporal lesions performed in infants produce greater effects on socioaffective behavior than similar lesions in adulthood and that infant monkeys with inferotemporal lesions exhibit social deficits that are resolved by adulthood. These results are relevant to three significant issues: (1) the role of the medial temporal and lateral temporal cortex in the symptoms of the Kluver-Bucy syndrome; (2) the role of age at injury in behavioral change after cerebral injuries; and (3) the importance of lesion locus and behavioral measure for recovery from infant and adult cerebral injury. © 2010 APA, all rights reserved.

Laminar Module Cascade from Layer 5 to 6 Implementing Cue-to-Target Conversion for Object Memory Retrieval in the Primate Temporal Cortex.

PubMed

Koyano, Kenji W; Takeda, Masaki; Matsui, Teppei; Hirabayashi, Toshiyuki; Ohashi, Yohei; Miyashita, Yasushi

2016-10-19

The cerebral cortex computes through the canonical microcircuit that connects six stacked layers; however, how cortical processing streams operate in vivo, particularly in the higher association cortex, remains elusive. By developing a novel MRI-assisted procedure that reliably localizes recorded single neurons at resolution of six individual layers in monkey temporal cortex, we show that transformation of representations from a cued object to a to-be-recalled object occurs at the infragranular layer in a visual cued-recall task. This cue-to-target conversion started in layer 5 and was followed by layer 6. Finally, a subset of layer 6 neurons exclusively encoding the sought target became phase-locked to surrounding field potentials at theta frequency, suggesting that this coordinated cell assembly implements cortical long-distance outputs of the recalled target. Thus, this study proposes a link from local computation spanning laminar modules of the temporal cortex to the brain-wide network for memory retrieval in primates. Copyright © 2016 Elsevier Inc. All rights reserved.

The cortical language circuit: from auditory perception to sentence comprehension.

PubMed

Friederici, Angela D

2012-05-01

Over the years, a large body of work on the brain basis of language comprehension has accumulated, paving the way for the formulation of a comprehensive model. The model proposed here describes the functional neuroanatomy of the different processing steps from auditory perception to comprehension as located in different gray matter brain regions. It also specifies the information flow between these regions, taking into account white matter fiber tract connections. Bottom-up, input-driven processes proceeding from the auditory cortex to the anterior superior temporal cortex and from there to the prefrontal cortex, as well as top-down, controlled and predictive processes from the prefrontal cortex back to the temporal cortex are proposed to constitute the cortical language circuit. Copyright © 2012 Elsevier Ltd. All rights reserved.

The perirhinal cortex of the rat is necessary for spatial memory retention long after but not soon after learning.

PubMed

Ramos, Juan M J; Vaquero, Joaquín M M

2005-09-15

Many observations in humans and experimental animals support the view that the hippocampus is critical immediately after learning in order for long-term memory formation to take place. However, exactly when the medial temporal cortices adjacent to the hippocampus are necessary for this process to occur normally is not yet well known. Using a spatial task, we studied whether the perirhinal cortex of rats is necessary to establish representations in long-term memory. Results showed that, in a spatial task sensitive to hippocampal lesions, control and perirhinal lesioned rats can both learn at the same rate (Experiment 1). Interestingly, a differential involvement of the perirhinal cortex in memory retention was observed as time passes after learning. Thus, 24 days following the end of learning, lesioned and control rats remembered the task perfectly as measured by a retraining test. In contrast, 74 days after the learning the perirhinal animals showed a profound impairment in the retention of the spatial information (Experiment 2). Taken together, these results suggest that the perirhinal region is critical for the formation of long-term spatial memory. However, its contribution to memory formation and retention is time-dependent, it being necessary only long after learning takes place and not during the phase immediately following acquisition.

Neurophysiological correlates of abnormal somatosensory temporal discrimination in dystonia.

PubMed

Antelmi, Elena; Erro, Roberto; Rocchi, Lorenzo; Liguori, Rocco; Tinazzi, Michele; Di Stasio, Flavio; Berardelli, Alfredo; Rothwell, John C; Bhatia, Kailash P

2017-01-01

Somatosensory temporal discrimination threshold is often prolonged in patients with dystonia. Previous evidence suggested that this might be caused by impaired somatosensory processing in the time domain. Here, we tested if other markers of reduced inhibition in the somatosensory system might also contribute to abnormal somatosensory temporal discrimination in dystonia. Somatosensory temporal discrimination threshold was measured in 19 patients with isolated cervical dystonia and 19 age-matched healthy controls. We evaluated temporal somatosensory inhibition using paired-pulse somatosensory evoked potentials, spatial somatosensory inhibition by measuring the somatosensory evoked potentials interaction between simultaneous stimulation of the digital nerves in thumb and index finger, and Gamma-aminobutyric acid-ergic (GABAergic) sensory inhibition using the early and late components of high-frequency oscillations in digital nerves somatosensory evoked potentials. When compared with healthy controls, dystonic patients had longer somatosensory temporal discrimination thresholds, reduced suppression of cortical and subcortical paired-pulse somatosensory evoked potentials, less spatial inhibition of simultaneous somatosensory evoked potentials, and a smaller area of the early component of the high-frequency oscillations. A logistic regression analysis found that paired pulse suppression of the N20 component at an interstimulus interval of 5 milliseconds and the late component of the high-frequency oscillations were independently related to somatosensory temporal discrimination thresholds. "Dystonia group" was also a predictor of enhanced somatosensory temporal discrimination threshold, indicating a dystonia-specific effect that independently influences this threshold. Increased somatosensory temporal discrimination threshold in dystonia is related to reduced activity of inhibitory circuits within the primary somatosensory cortex. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Differentiability of simulated MEG hippocampal, medial temporal and neocortical temporal epileptic spike activity.

PubMed

Stephen, Julia M; Ranken, Doug M; Aine, Cheryl J; Weisend, Michael P; Shih, Jerry J

2005-12-01

Previous studies have shown that magnetoencephalography (MEG) can measure hippocampal activity, despite the cylindrical shape and deep location in the brain. The current study extended this work by examining the ability to differentiate the hippocampal subfields, parahippocampal cortex, and neocortical temporal sources using simulated interictal epileptic activity. A model of the hippocampus was generated on the MRIs of five subjects. CA1, CA3, and dentate gyrus of the hippocampus were activated as well as entorhinal cortex, presubiculum, and neocortical temporal cortex. In addition, pairs of sources were activated sequentially to emulate various hypotheses of mesial temporal lobe seizure generation. The simulated MEG activity was added to real background brain activity from the five subjects and modeled using a multidipole spatiotemporal modeling technique. The waveforms and source locations/orientations for hippocampal and parahippocampal sources were differentiable from neocortical temporal sources. In addition, hippocampal and parahippocampal sources were differentiated to varying degrees depending on source. The sequential activation of hippocampal and parahippocampal sources was adequately modeled by a single source; however, these sources were not resolvable when they overlapped in time. These results suggest that MEG has the sensitivity to distinguish parahippocampal and hippocampal spike generators in mesial temporal lobe epilepsy.

Integrating automatic and controlled processes into neurocognitive models of social cognition.

PubMed

Satpute, Ajay B; Lieberman, Matthew D

2006-03-24

Interest in the neural systems underlying social perception has expanded tremendously over the past few decades. However, gaps between behavioral literatures in social perception and neuroscience are still abundant. In this article, we apply the concept of dual-process models to neural systems in an effort to bridge the gap between many of these behavioral studies and neural systems underlying social perception. We describe and provide support for a neural division between reflexive and reflective systems. Reflexive systems correspond to automatic processes and include the amygdala, basal ganglia, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, and lateral temporal cortex. Reflective systems correspond to controlled processes and include lateral prefrontal cortex, posterior parietal cortex, medial prefrontal cortex, rostral anterior cingulate cortex, and the hippocampus and surrounding medial temporal lobe region. This framework is considered to be a working model rather than a finished product. Finally, the utility of this model and its application to other social cognitive domains such as Theory of Mind are discussed.

Hippocampal and Parahippocampal Volumes in Schizophrenia: A Structural MRI Study

PubMed Central

Sim, Kang; DeWitt, Iain; Ditman, Tali; Zalesak, Martin; Greenhouse, Ian; Goff, Donald; Weiss, Anthony P; Heckers, Stephan

2006-01-01

Smaller medial temporal lobe volume is a frequent finding in studies of patients with schizophrenia, but the relative contributions of the hippocampus and three surrounding cortical regions (entorhinal cortex, perirhinal cortex, and parahippocampal cortex) are poorly understood. We tested the hypothesis that the volumes of medial temporal lobe regions are selectively changed in schizophrenia. We studied 19 male patients with schizophrenia and 19 age-matched male control subjects. Hippocampal and cortical volumes were estimated using a three-dimensional morphometric protocol for the analysis of high-resolution structural magnetic resonance images, and repeated measures ANOVA was used to test for region-specific differences. Patients had smaller overall medial temporal lobe volumes compared to controls. The volume difference was not specific for either region or hemisphere. The finding of smaller medial temporal lobe volumes in the absence of regional specificity has important implications for studying the functional role of the hippocampus and surrounding cortical regions in schizophrenia. PMID:16319377

Differential involvement of the posterior temporal cortex in mentalizing but not perspective taking

PubMed Central

Aumann, Carolin; Santos, Natacha S.; Bewernick, Bettina H.; Eickhoff, Simon B.; Newen, Albert; Shah, N. Jon; Fink, Gereon R.; Vogeley, Kai

2008-01-01

Understanding and predicting other people's mental states and behavior are important prerequisites for social interactions. The capacity to attribute mental states such as desires, thoughts or intentions to oneself or others is referred to as mentalizing. The right posterior temporal cortex at the temporal–parietal junction has been associated with mentalizing but also with taking someone else's spatial perspective onto the world—possibly an important prerequisite for mentalizing. Here, we directly compared the neural correlates of mentalizing and perspective taking using the same stimulus material. We found significantly increased neural activity in the right posterior segment of the superior temporal sulcus only during mentalizing but not perspective taking. Our data further clarify the role of the posterior temporal cortex in social cognition by showing that it is involved in processing information from socially salient visual cues in situations that require the inference about other people's mental states. PMID:19015120

Reading Without the Left Ventral Occipito-Temporal Cortex

ERIC Educational Resources Information Center

Seghier, Mohamed L.; Neufeld, Nicholas H.; Zeidman, Peter; Leff, Alex P.; Mechelli, Andrea; Nagendran, Arjuna; Riddoch, Jane M.; Humphreys, Glyn W.; Price, Cathy J.

2012-01-01

The left ventral occipito-temporal cortex (LvOT) is thought to be essential for the rapid parallel letter processing that is required for skilled reading. Here we investigate whether rapid written word identification in skilled readers can be supported by neural pathways that do not involve LvOT. Hypotheses were derived from a stroke patient who…

Differential neural responses to food images in women with bulimia versus anorexia nervosa.

PubMed

Brooks, Samantha J; O'Daly, Owen G; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C R; Schiöth, Helgi B; Treasure, Janet; Campbell, Iain C

2011-01-01

Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.

The Michelin red guide of the brain: role of dopamine in goal-oriented navigation.

PubMed

Retailleau, Aude; Boraud, Thomas

2014-01-01

Spatial learning has been recognized over the years to be under the control of the hippocampus and related temporal lobe structures. Hippocampal damage often causes severe impairments in the ability to learn and remember a location in space defined by distal visual cues. Such cognitive disabilities are found in Parkinsonian patients. We recently investigated the role of dopamine in navigation in the 6-Hydroxy-dopamine (6-OHDA) rat, a model of Parkinson's disease (PD) commonly used to investigate the pathophysiology of dopamine depletion (Retailleau et al., 2013). We demonstrated that dopamine (DA) is essential to spatial learning as its depletion results in spatial impairments. Our results showed that the behavioral effect of DA depletion is correlated with modification of the neural encoding of spatial features and decision making processes in hippocampus. However, the origin of these alterations in the neural processing of the spatial information needs to be clarified. It could result from a local effect: dopamine depletion disturbs directly the processing of relevant spatial information at hippocampal level. Alternatively, it could result from a more distributed network effect: dopamine depletion elsewhere in the brain (entorhinal cortex, striatum, etc.) modifies the way hippocampus processes spatial information. Recent experimental evidence in rodents, demonstrated indeed, that other brain areas are involved in the acquisition of spatial information. Amongst these, the cortex-basal ganglia (BG) loop is known to be involved in reinforcement learning and has been identified as an important contributor to spatial learning. In particular, it has been shown that altered activity of the BG striatal complex can impair the ability to perform spatial learning tasks. The present review provides a glimpse of the findings obtained over the past decade that support a dialog between these two structures during spatial learning under DA control.

Neurogranin binds α-synuclein in the human superior temporal cortex and interaction is decreased in Parkinson's disease.

PubMed

Koob, Andrew O; Shaked, Gideon M; Bender, Andreas; Bisquertt, Alejandro; Rockenstein, Edward; Masliah, Eliezer

2014-12-03

Neurogranin is a calmodulin binding protein that has been implicated in learning and memory, long-term potentiation and synaptic plasticity. Neurons expressing neurogranin in the cortex degenerate in late stages of Parkinson's disease with widespread α-synuclein pathology. While analyzing neurogranin gene expression levels through rtPCR in brains of mouse models overexpressing human α-synuclein, we found levels were elevated 2.5 times when compared to nontransgenic animals. Immunohistochemistry in the cortex revealed colocalization between α-synuclein and neurogranin in mouse transgenics when compared to control mice. Coimmunoprecipitation studies in the superior temporal cortex in humans confirmed interaction between α-synuclein and neurogranin, and decreased interaction between α-synuclein and neurogranin was noticed in patients diagnosed with Parkinson's disease when compared to normal control brains. Additionally, phosphorylated neurogranin levels were also decreased in the human superior temporal cortex in patients diagnosed with Parkinson's disease and patients diagnosed with dementia with Lewy bodies. Here, we show for the first time that neurogranin binds to α-synuclein in the human cortex, and this interaction decreases in Parkinson's disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurogranin binds α-synuclein in the human superior temporal cortex and interaction is decreased in Parkinson’s disease

PubMed Central

Koob, Andrew O.; Shaked, Gideon M.; Bender, Andreas; Bisquertt, Alejandro; Rockenstein, Edward; Masliah, Eliezer

2016-01-01

Neurogranin is a calmodulin binding protein that has been implicated in learning and memory, long-term potentiation and synaptic plasticity. Neurons expressing neurogranin in the cortex degenerate in late stages of Parkinson’s disease with widespread α-synuclein pathology. While analyzing neurogranin gene expression levels through rtPCR in brains of mouse models overexpressing human α-synuclein, we found levels were elevated 2.5 times when compared to nontransgenic animals. Immunohistochemistry in the cortex revealed colocalization between α-synuclein and neurogranin in mouse transgenics when compared to control mice. Coimmunoprecipitation studies in the superior temporal cortex in humans confirmed interaction between α-synuclein and neurogranin, and decreased interaction between α-synuclein and neurogranin was noticed in patients diagnosed with Parkinson’s disease when compared to normal control brains. Additionally, phosphorylated neurogranin levels were also decreased in the human superior temporal cortex in patients diagnosed with Parkinson’s disease and patients diagnosed with dementia with Lewy bodies. Here, we show for the first time that neurogranin binds to α-synuclein in the human cortex, and this interaction decreases in Parkinson’s disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory. PMID:25446004

Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities.

PubMed

Marisco, Patricia C; Carvalho, Fabiano B; Rosa, Michelle M; Girardi, Bruna A; Gutierres, Jessié M; Jaques, Jeandre A S; Salla, Ana P S; Pimentel, Víctor C; Schetinger, Maria Rosa C; Leal, Daniela B R; Mello, Carlos F; Rubin, Maribel A

2013-08-01

Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.

Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

PubMed

Spalletta, Gianfranco; Cravello, Luca; Gianni, Walter; Piras, Federica; Iorio, Mariangela; Cacciari, Claudia; Casini, Anna Rosa; Chiapponi, Chiara; Sancesario, Giuseppe; Fratangeli, Claudia; Orfei, Maria Donata; Caltagirone, Carlo; Piras, Fabrizio

2016-01-01

Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

Neural correlates of coherent and biological motion perception in autism.

PubMed

Koldewyn, Kami; Whitney, David; Rivera, Susan M

2011-09-01

Recent evidence suggests those with autism may be generally impaired in visual motion perception. To examine this, we investigated both coherent and biological motion processing in adolescents with autism employing both psychophysical and fMRI methods. Those with autism performed as well as matched controls during coherent motion perception but had significantly higher thresholds for biological motion perception. The autism group showed reduced posterior Superior Temporal Sulcus (pSTS), parietal and frontal activity during a biological motion task while showing similar levels of activity in MT+/V5 during both coherent and biological motion trials. Activity in MT+/V5 was predictive of individual coherent motion thresholds in both groups. Activity in dorsolateral prefrontal cortex (DLPFC) and pSTS was predictive of biological motion thresholds in control participants but not in those with autism. Notably, however, activity in DLPFC was negatively related to autism symptom severity. These results suggest that impairments in higher-order social or attentional networks may underlie visual motion deficits observed in autism. © 2011 Blackwell Publishing Ltd.

Neural correlates of coherent and biological motion perception in autism

PubMed Central

Koldewyn, Kami; Whitney, David; Rivera, Susan M.

2011-01-01

Recent evidence suggests those with autism may be generally impaired in visual motion perception. To examine this, we investigated both coherent and biological motion processing in adolescents with autism employing both psychophysical and fMRI methods. Those with autism performed as well as matched controls during coherent motion perception but had significantly higher thresholds for biological motion perception. The autism group showed reduced posterior Superior Temporal Sulcus (pSTS), parietal and frontal activity during a biological motion task while showing similar levels of activity in MT+/V5 during both coherent and biological motion trials. Activity in MT+/V5 was predictive of individual coherent motion thresholds in both groups. Activity in dorsolateral prefrontal cortex (DLPFC) and pSTS was predictive of biological motion thresholds in control participants but not in those with autism. Notably, however, activity in DLPFC was negatively related to autism symptom severity. These results suggest that impairments in higher-order social or attentional networks may underlie visual motion deficits observed in autism. PMID:21884323

Cortical Thickness and Episodic Memory Impairment in Systemic Lupus Erythematosus.

PubMed

Bizzo, Bernardo Canedo; Sanchez, Tiago Arruda; Tukamoto, Gustavo; Zimmermann, Nicolle; Netto, Tania Maria; Gasparetto, Emerson Leandro

2017-01-01

The purpose of this study was to investigate differences in brain cortical thickness of systemic lupus erythematosus (SLE) patients with and without episodic memory impairment and healthy controls. We studied 51 patients divided in 2 groups (SLE with episodic memory deficit, n = 17; SLE without episodic memory deficit, n = 34) by the Rey Auditory Verbal Learning Test and 34 healthy controls. Groups were paired based on sex, age, education, Mini-Mental State Examination score, and accumulation of disease burden. Cortical thickness from magnetic resonance imaging scans was determined using the FreeSurfer software package. SLE patients with episodic memory deficits presented reduced cortical thickness in the left supramarginal cortex and superior temporal gyrus when compared to the control group and in the right superior frontal, caudal, and rostral middle frontal and precentral gyri when compared to the SLE group without episodic memory impairment considering time since diagnosis of SLE as covaried. There were no significant differences in the cortical thickness between the SLE without episodic memory and control groups. Different memory-related cortical regions thinning were found in the episodic memory deficit group when individually compared to the groups of patients without memory impairment and healthy controls. Copyright © 2016 by the American Society of Neuroimaging.

Investigating virtual reality navigation in amnestic mild cognitive impairment using fMRI.

PubMed

Migo, E M; O'Daly, O; Mitterschiffthaler, M; Antonova, E; Dawson, G R; Dourish, C T; Craig, K J; Simmons, A; Wilcock, G K; McCulloch, E; Jackson, S H D; Kopelman, M D; Williams, S C R; Morris, R G

2016-01-01

Spatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.

Articulatory movements modulate auditory responses to speech

PubMed Central

Agnew, Z.K.; McGettigan, C.; Banks, B.; Scott, S.K.

2013-01-01

Production of actions is highly dependent on concurrent sensory information. In speech production, for example, movement of the articulators is guided by both auditory and somatosensory input. It has been demonstrated in non-human primates that self-produced vocalizations and those of others are differentially processed in the temporal cortex. The aim of the current study was to investigate how auditory and motor responses differ for self-produced and externally produced speech. Using functional neuroimaging, subjects were asked to produce sentences aloud, to silently mouth while listening to a different speaker producing the same sentence, to passively listen to sentences being read aloud, or to read sentences silently. We show that that separate regions of the superior temporal cortex display distinct response profiles to speaking aloud, mouthing while listening, and passive listening. Responses in anterior superior temporal cortices in both hemispheres are greater for passive listening compared with both mouthing while listening, and speaking aloud. This is the first demonstration that articulation, whether or not it has auditory consequences, modulates responses of the dorsolateral temporal cortex. In contrast posterior regions of the superior temporal cortex are recruited during both articulation conditions. In dorsal regions of the posterior superior temporal gyrus, responses to mouthing and reading aloud were equivalent, and in more ventral posterior superior temporal sulcus, responses were greater for reading aloud compared with mouthing while listening. These data demonstrate an anterior–posterior division of superior temporal regions where anterior fields are suppressed during motor output, potentially for the purpose of enhanced detection of the speech of others. We suggest posterior fields are engaged in auditory processing for the guidance of articulation by auditory information. PMID:22982103

Right anterior superior temporal activation predicts auditory sentence comprehension following aphasic stroke.

PubMed

Crinion, Jenny; Price, Cathy J

2005-12-01

Previous studies have suggested that recovery of speech comprehension after left hemisphere infarction may depend on a mechanism in the right hemisphere. However, the role that distinct right hemisphere regions play in speech comprehension following left hemisphere stroke has not been established. Here, we used functional magnetic resonance imaging (fMRI) to investigate narrative speech activation in 18 neurologically normal subjects and 17 patients with left hemisphere stroke and a history of aphasia. Activation for listening to meaningful stories relative to meaningless reversed speech was identified in the normal subjects and in each patient. Second level analyses were then used to investigate how story activation changed with the patients' auditory sentence comprehension skills and surprise story recognition memory tests post-scanning. Irrespective of lesion site, performance on tests of auditory sentence comprehension was positively correlated with activation in the right lateral superior temporal region, anterior to primary auditory cortex. In addition, when the stroke spared the left temporal cortex, good performance on tests of auditory sentence comprehension was also correlated with the left posterior superior temporal cortex (Wernicke's area). In distinct contrast to this, good story recognition memory predicted left inferior frontal and right cerebellar activation. The implication of this double dissociation in the effects of auditory sentence comprehension and story recognition memory is that left frontal and left temporal activations are dissociable. Our findings strongly support the role of the right temporal lobe in processing narrative speech and, in particular, auditory sentence comprehension following left hemisphere aphasic stroke. In addition, they highlight the importance of the right anterior superior temporal cortex where the response was dissociated from that in the left posterior temporal lobe.

Revealing and quantifying the impaired phonological analysis underpinning impaired comprehension in Wernicke's aphasia.

PubMed

Robson, Holly; Keidel, James L; Ralph, Matthew A Lambon; Sage, Karen

2012-01-01

Wernicke's aphasia is a condition which results in severely disrupted language comprehension following a lesion to the left temporo-parietal region. A phonological analysis deficit has traditionally been held to be at the root of the comprehension impairment in Wernicke's aphasia, a view consistent with current functional neuroimaging which finds areas in the superior temporal cortex responsive to phonological stimuli. However behavioural evidence to support the link between a phonological analysis deficit and auditory comprehension has not been yet shown. This study extends seminal work by Blumstein, Baker, and Goodglass (1977) to investigate the relationship between acoustic-phonological perception, measured through phonological discrimination, and auditory comprehension in a case series of Wernicke's aphasia participants. A novel adaptive phonological discrimination task was used to obtain reliable thresholds of the phonological perceptual distance required between nonwords before they could be discriminated. Wernicke's aphasia participants showed significantly elevated thresholds compared to age and hearing matched control participants. Acoustic-phonological thresholds correlated strongly with auditory comprehension abilities in Wernicke's aphasia. In contrast, nonverbal semantic skills showed no relationship with auditory comprehension. The results are evaluated in the context of recent neurobiological models of language and suggest that impaired acoustic-phonological perception underlies the comprehension impairment in Wernicke's aphasia and favour models of language which propose a leftward asymmetry in phonological analysis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI

PubMed Central

Tomassy, Giulio Srubek; De Leonibus, Elvira; Jabaudon, Denis; Lodato, Simona; Alfano, Christian; Mele, Andrea; Macklis, Jeffrey D.; Studer, Michèle

2010-01-01

Transcription factors with gradients of expression in neocortical progenitors give rise to distinct motor and sensory cortical areas by controlling the area-specific differentiation of distinct neuronal subtypes. However, the molecular mechanisms underlying this area-restricted control are still unclear. Here, we show that COUP-TFI controls the timing of birth and specification of corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a CSMN differentiation program. Loss of COUP-TFI function causes an area-specific premature generation of neurons with cardinal features of CSMN, which project to subcerebral structures, including the spinal cord. Concurrently, genuine CSMN differentiate imprecisely and do not project beyond the pons, together resulting in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of-function. Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise. PMID:20133588

How do auditory cortex neurons represent communication sounds?

PubMed

Gaucher, Quentin; Huetz, Chloé; Gourévitch, Boris; Laudanski, Jonathan; Occelli, Florian; Edeline, Jean-Marc

2013-11-01

A major goal in auditory neuroscience is to characterize how communication sounds are represented at the cortical level. The present review aims at investigating the role of auditory cortex in the processing of speech, bird songs and other vocalizations, which all are spectrally and temporally highly structured sounds. Whereas earlier studies have simply looked for neurons exhibiting higher firing rates to particular conspecific vocalizations over their modified, artificially synthesized versions, more recent studies determined the coding capacity of temporal spike patterns, which are prominent in primary and non-primary areas (and also in non-auditory cortical areas). In several cases, this information seems to be correlated with the behavioral performance of human or animal subjects, suggesting that spike-timing based coding strategies might set the foundations of our perceptive abilities. Also, it is now clear that the responses of auditory cortex neurons are highly nonlinear and that their responses to natural stimuli cannot be predicted from their responses to artificial stimuli such as moving ripples and broadband noises. Since auditory cortex neurons cannot follow rapid fluctuations of the vocalizations envelope, they only respond at specific time points during communication sounds, which can serve as temporal markers for integrating the temporal and spectral processing taking place at subcortical relays. Thus, the temporal sparse code of auditory cortex neurons can be considered as a first step for generating high level representations of communication sounds independent of the acoustic characteristic of these sounds. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives". Copyright © 2013 Elsevier B.V. All rights reserved.

Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex

NASA Technical Reports Server (NTRS)

Chen, W. R.; Lee, S.; Kato, K.; Spencer, D. D.; Shepherd, G. M.; Williamson, A.

1996-01-01

The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage.

PubMed

Naylor, Jennifer C; Hulette, Christine M; Steffens, David C; Shampine, Lawrence J; Ervin, John F; Payne, Victoria M; Massing, Mark W; Kilts, Jason D; Strauss, Jennifer L; Calhoun, Patrick S; Calnaido, Rohana P; Blazer, Daniel G; Lieberman, Jeffrey A; Madison, Roger D; Marx, Christine E

2008-08-01

It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

Word or Word-Like? Dissociating Orthographic Typicality from Lexicality in the Left Occipito-Temporal Cortex

ERIC Educational Resources Information Center

Woollams, Anna M.; Silani, Giorgia; Okada, Kayoko; Patterson, Karalyn; Price, Cathy J.

2011-01-01

Prior lesion and functional imaging studies have highlighted the importance of the left ventral occipito-temporal (LvOT) cortex for visual word recognition. Within this area, there is a posterior-anterior hierarchy of subregions that are specialized for different stages of orthographic processing. The aim of the present fMRI study was to…

Pairing tone trains with vagus nerve stimulation induces temporal plasticity in auditory cortex.

PubMed

Shetake, Jai A; Engineer, Navzer D; Vrana, Will A; Wolf, Jordan T; Kilgard, Michael P

2012-01-01

The selectivity of neurons in sensory cortex can be modified by pairing neuromodulator release with sensory stimulation. Repeated pairing of electrical stimulation of the cholinergic nucleus basalis, for example, induces input specific plasticity in primary auditory cortex (A1). Pairing nucleus basalis stimulation (NBS) with a tone increases the number of A1 neurons that respond to the paired tone frequency. Pairing NBS with fast or slow tone trains can respectively increase or decrease the ability of A1 neurons to respond to rapidly presented tones. Pairing vagus nerve stimulation (VNS) with a single tone alters spectral tuning in the same way as NBS-tone pairing without the need for brain surgery. In this study, we tested whether pairing VNS with tone trains can change the temporal response properties of A1 neurons. In naïve rats, A1 neurons respond strongly to tones repeated at rates up to 10 pulses per second (pps). Repeatedly pairing VNS with 15 pps tone trains increased the temporal following capacity of A1 neurons and repeatedly pairing VNS with 5 pps tone trains decreased the temporal following capacity of A1 neurons. Pairing VNS with tone trains did not alter the frequency selectivity or tonotopic organization of auditory cortex neurons. Since VNS is well tolerated by patients, VNS-tone train pairing represents a viable method to direct temporal plasticity in a variety of human conditions associated with temporal processing deficits. Copyright © 2011 Elsevier Inc. All rights reserved.

Proton magnetic resonance spectroscopy (MRS) in on-line game addiction

PubMed Central

Han, Doug Hyun; Lee, Young Sik; Shi, Xianfeng; Renshaw, Perry F.

2015-01-01

Recent brain imaging studies suggested that both the frontal and temporal cortices are important candidate areas for mediating the symptoms of internet addiction. We hypothesized that deficits of prefrontal and temporal cortical function in patients with on-line game addiction (PGA) would be reflected in decreased levels of N-acetyl aspartate (NAA) and cytosolic, choline containing compound (Cho). Seventy three young PGA and 38 age and sex matched healthy control subjects were recruited in the study. Structural MR and 1H MRS data were acquired using a 3.0 T MRI scanner. Voxels were sequentially placed in right frontal cortex and right medial temporal cortices. In the right frontal cortex, the levels of NAA in PGA were lower than those in healthy controls. In the medial temporal cortex, the levels of Cho in PGA participants were lower than those observed in healthy controls. The Young Internet Addiction Scale (YIAS) scores and perseverative responses in PGA were negatively correlated with the level of NAA in right frontal cortex. The Beck Depressive Inventory (BDI) scores in the PGA cohort were negatively correlated with Cho levels in the right temporal lobe. To the best of our knowledge, this is the first MRS study of individuals with on-line game addiction. Although, the subjects with on-line game addiction in the current study were free from psychiatric co-morbidity, patients with on-line game addiction appear to share characteristics with ADHD and MDD in terms of neurochemical changes in frontal and temporal cortices. PMID:25088284

Encoding of Natural Sounds at Multiple Spectral and Temporal Resolutions in the Human Auditory Cortex

PubMed Central

Santoro, Roberta; Moerel, Michelle; De Martino, Federico; Goebel, Rainer; Ugurbil, Kamil; Yacoub, Essa; Formisano, Elia

2014-01-01

Functional neuroimaging research provides detailed observations of the response patterns that natural sounds (e.g. human voices and speech, animal cries, environmental sounds) evoke in the human brain. The computational and representational mechanisms underlying these observations, however, remain largely unknown. Here we combine high spatial resolution (3 and 7 Tesla) functional magnetic resonance imaging (fMRI) with computational modeling to reveal how natural sounds are represented in the human brain. We compare competing models of sound representations and select the model that most accurately predicts fMRI response patterns to natural sounds. Our results show that the cortical encoding of natural sounds entails the formation of multiple representations of sound spectrograms with different degrees of spectral and temporal resolution. The cortex derives these multi-resolution representations through frequency-specific neural processing channels and through the combined analysis of the spectral and temporal modulations in the spectrogram. Furthermore, our findings suggest that a spectral-temporal resolution trade-off may govern the modulation tuning of neuronal populations throughout the auditory cortex. Specifically, our fMRI results suggest that neuronal populations in posterior/dorsal auditory regions preferably encode coarse spectral information with high temporal precision. Vice-versa, neuronal populations in anterior/ventral auditory regions preferably encode fine-grained spectral information with low temporal precision. We propose that such a multi-resolution analysis may be crucially relevant for flexible and behaviorally-relevant sound processing and may constitute one of the computational underpinnings of functional specialization in auditory cortex. PMID:24391486

Altered resting-state functional activity in isolated pontine infarction patients with pathological laughing and crying.

PubMed

Liu, Tao; Li, Jianjun; Huang, Shixiong; Li, Changqinq; Zhao, Zhongyan; Wen, Guoqiang; Chen, Feng

2017-10-13

We used resting-state functional magnetic resonance imaging to investigate the global spontaneous neural activity involved in pathological laughing and crying after stroke. Twelve pathological laughing and crying patients with isolated pontine infarction were included, along with 12 age- and gender-matched acute isolated pontine infarction patients without pathological laughing and crying, and 12 age- and gender-matched healthy controls. We examined both the amplitude of low-frequency fluctuation and the regional homogeneity in order to comprehensively evaluate the intrinsic activity in patients with post-stroke pathological laughing and crying. In the post-stroke pathological laughing and crying group, changes in these measures were observed mainly in components of the default mode network (medial prefrontal cortex/anterior cingulate cortex, middle temporal gyrus, inferior temporal gyrus, superior frontal gyrus, middle frontal gyrus and inferior parietal lobule), sensorimotor network (supplementary motor area, precentral gyrus and paracentral lobule), affective network (medial prefrontal cortex/anterior cingulate cortex, parahippocampal gyrus, middle temporal gyrus and inferior temporal gyrus) and cerebellar lobes (cerebellum posterior lobe). We therefore speculate that when disinhibition of the volitional system is lost, increased activation of the emotional system causes pathological laughing and crying.

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function

PubMed Central

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L.; Rajah, M. Natasha

2016-01-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. PMID:25882039

Emotional modulation of experimental pain: a source imaging study of laser evoked potentials

PubMed Central

Stancak, Andrej; Fallon, Nicholas

2013-01-01

Negative emotions have been shown to augment experimental pain. As induced emotions alter brain activity, it is not clear whether pain augmentation during noxious stimulation would be related to neural activation existing prior to onset of a noxious stimulus or alternatively, whether emotional stimuli would only alter neural activity during the period of nociceptive processing. We analyzed the spatio-temporal patterns of laser evoked potentials (LEPs) occurring prior to and during the period of cortical processing of noxious laser stimuli during passive viewing of negative, positive, or neutral emotional pictures. Independent component analysis (ICA) was applied to series of source activation volumes, reconstructed using local autoregressive average model (LAURA). Pain was the strongest when laser stimuli were associated with negative emotional pictures. Prior to laser stimulus and during the first 100 ms after onset of laser stimulus, activations were seen in the left and right medial temporal cortex, cerebellum, posterior cingulate, and rostral cingulate/prefrontal cortex. In all these regions, positive or neutral pictures showed stronger activations than negative pictures. During laser stimulation, activations in the right and left anterior insula, temporal cortex and right anterior and posterior parietal cortex were stronger during negative than neutral or positive emotional pictures. Results suggest that negative emotional stimuli increase activation in the left and right anterior insula and temporal cortex, and right posterior and anterior parietal cortex only during the period of nociceptive processing. The role of background brain activation in emotional modulation of pain appears to be only permissive, and consisting in attenuation of activation in structures maintaining the resting state of the brain. PMID:24062659

Cholinergic Neuromodulation Controls Directed Temporal Communication in Neocortex in Vitro

PubMed Central

Roopun, Anita K.; LeBeau, Fiona E.N.; Rammell, James; Cunningham, Mark O.; Traub, Roger D.; Whittington, Miles A.

2010-01-01

Acetylcholine is the primary neuromodulator involved in cortical arousal in mammals. Cholinergic modulation is involved in conscious awareness, memory formation and attention – processes that involve intercommunication between different cortical regions. Such communication is achieved in part through temporal structuring of neuronal activity by population rhythms, particularly in the beta and gamma frequency ranges (12–80 Hz). Here we demonstrate, using in vitro and in silico models, that spectrally identical patterns of beta2 and gamma rhythms are generated in primary sensory areas and polymodal association areas by fundamentally different local circuit mechanisms: Glutamatergic excitation induced beta2 frequency population rhythms only in layer 5 association cortex whereas cholinergic neuromodulation induced this rhythm only in layer 5 primary sensory cortex. This region-specific sensitivity of local circuits to cholinergic modulation allowed for control of the extent of cortical temporal interactions. Furthermore, the contrasting mechanisms underlying these beta2 rhythms produced a high degree of directionality, favouring an influence of association cortex over primary auditory cortex. PMID:20407636

Associative-memory representations emerge as shared spatial patterns of theta activity spanning the primate temporal cortex

PubMed Central

Nakahara, Kiyoshi; Adachi, Ken; Kawasaki, Keisuke; Matsuo, Takeshi; Sawahata, Hirohito; Majima, Kei; Takeda, Masaki; Sugiyama, Sayaka; Nakata, Ryota; Iijima, Atsuhiko; Tanigawa, Hisashi; Suzuki, Takafumi; Kamitani, Yukiyasu; Hasegawa, Isao

2016-01-01

Highly localized neuronal spikes in primate temporal cortex can encode associative memory; however, whether memory formation involves area-wide reorganization of ensemble activity, which often accompanies rhythmicity, or just local microcircuit-level plasticity, remains elusive. Using high-density electrocorticography, we capture local-field potentials spanning the monkey temporal lobes, and show that the visual pair-association (PA) memory is encoded in spatial patterns of theta activity in areas TE, 36, and, partially, in the parahippocampal cortex, but not in the entorhinal cortex. The theta patterns elicited by learned paired associates are distinct between pairs, but similar within pairs. This pattern similarity, emerging through novel PA learning, allows a machine-learning decoder trained on theta patterns elicited by a particular visual item to correctly predict the identity of those elicited by its paired associate. Our results suggest that the formation and sharing of widespread cortical theta patterns via learning-induced reorganization are involved in the mechanisms of associative memory representation. PMID:27282247

Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA-AA criteria.

PubMed

Ito, Kimiteru; Shimano, Yasumasa; Imabayashi, Etsuko; Nakata, Yasuhiro; Omachi, Yoshie; Sato, Noriko; Arima, Kunimasa; Matsuda, Hiroshi

2014-10-01

The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with 18F-FDG PET and (99m)Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. The regions with better interobserver reliability between 18F-FDG PET and (99m)Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m)Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between 18F-FDG PET and (99m)Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. The degree of uptake on 18F-FDG PET and (99m)Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F-FDG PET and (99m)Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.

Cancer 'survivor-care': II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment).

PubMed

Raffa, R B

2013-08-01

Cancer chemotherapy-associated cognitive impairments (termed 'chemo-fog' or 'chemo-brain'), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. Although a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for 'top-down control' of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex in addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation. © 2013 John Wiley & Sons Ltd.

Depression and anxious apprehension distinguish frontocingulate cortical activity during top-down attentional control.

PubMed

Silton, Rebecca Levin; Heller, Wendy; Engels, Anna S; Towers, David N; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2011-05-01

A network consisting of left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC) has been implicated in top-down attentional control. Few studies have systematically investigated how this network is altered in psychopathology, despite evidence that depression and anxiety are associated with attentional control impairments. Functional MRI and dense-array event-related brain potential (ERP) data were collected in separate sessions from 100 participants during a color-word Stroop task. Functional MRI results guided ERP source modeling to characterize the time course of activity in LDLPFC (300-440 ms) and dACC (520-680 ms). At low levels of depression, LDLPFC activity was indirectly related to Stroop interference and only via dACC activity. In contrast, at high levels of depression, dACC did not play an intervening role, and increased LDLPFC activity was directly related to decreased Stroop interference. Specific to high levels of anxious apprehension, higher dACC activity was related to more Stroop interference. Results indicate that depression and anxious apprehension modulate temporally and functionally distinct aspects of the frontocingulate network involved in top-down attention control.

Neural basis for recognition confidence in younger and older adults.

PubMed

Chua, Elizabeth F; Schacter, Daniel L; Sperling, Reisa A

2009-03-01

Although several studies have examined the neural basis for age-related changes in objective memory performance, less is known about how the process of memory monitoring changes with aging. The authors used functional magnetic resonance imaging to examine retrospective confidence in memory performance in aging. During low confidence, both younger and older adults showed behavioral evidence that they were guessing during recognition and that they were aware they were guessing when making confidence judgments. Similarly, both younger and older adults showed increased neural activity during low- compared to high-confidence responses in the lateral prefrontal cortex, anterior cingulate cortex, and left intraparietal sulcus. In contrast, older adults showed more high-confidence errors than younger adults. Younger adults showed greater activity for high compared to low confidence in medial temporal lobe structures, but older adults did not show this pattern. Taken together, these findings may suggest that impairments in the confidence-accuracy relationship for memory in older adults, which are often driven by high-confidence errors, may be primarily related to altered neural signals associated with greater activity for high-confidence responses.

Neural basis for recognition confidence in younger and older adults

PubMed Central

Chua, Elizabeth F.; Schacter, Daniel L.; Sperling, Reisa A.

2008-01-01

Although several studies have examined the neural basis for age-related changes in objective memory performance, less is known about how the process of memory monitoring changes with aging. We used fMRI to examine retrospective confidence in memory performance in aging. During low confidence, both younger and older adults showed behavioral evidence that they were guessing during recognition, and that they were aware they were guessing when making confidence judgments. Similarly, both younger and older adults showed increased neural activity during low compared to high confidence responses in lateral prefrontal cortex, anterior cingulate cortex, and left intraparietal sulcus. In contrast, older adults showed more high confidence errors than younger adults. Younger adults showed greater activity for high compared to low confidence in medial temporal lobe structures, but older adults did not show this pattern. Taken together, these findings may suggest that impairments in the confidence-accuracy relationship for memory in older adults, which are often driven by high confidence errors, may be primarily related to altered neural signals associated with greater activity for high confidence responses. PMID:19290745

Neural correlates of semantic associations in patients with schizophrenia.

PubMed

Sass, Katharina; Heim, Stefan; Sachs, Olga; Straube, Benjamin; Schneider, Frank; Habel, Ute; Kircher, Tilo

2014-03-01

Patients with schizophrenia have semantic processing disturbances leading to expressive language deficits (formal thought disorder). The underlying pathology has been related to alterations in the semantic network and its neural correlates. Moreover, crossmodal processing, an important aspect of communication, is impaired in schizophrenia. Here we investigated specific processing abnormalities in patients with schizophrenia with regard to modality and semantic distance in a semantic priming paradigm. Fourteen patients with schizophrenia and fourteen demographically matched controls made visual lexical decisions on successively presented word-pairs (SOA = 350 ms) with direct or indirect relations, unrelated word-pairs, and pseudoword-target stimuli during fMRI measurement. Stimuli were presented in a unimodal (visual) or crossmodal (auditory-visual) fashion. On the neural level, the effect of semantic relation indicated differences (patients > controls) within the right angular gyrus and precuneus. The effect of modality revealed differences (controls > patients) within the left superior frontal, middle temporal, inferior occipital, right angular gyri, and anterior cingulate cortex. Semantic distance (direct vs. indirect) induced distinct activations within the left middle temporal, fusiform gyrus, right precuneus, and thalamus with patients showing fewer differences between direct and indirect word-pairs. The results highlight aberrant priming-related brain responses in patients with schizophrenia. Enhanced activation for patients possibly reflects deficits in semantic processes that might be caused by a delayed and enhanced spread of activation within the semantic network. Modality-specific decreases of activation in patients might be related to impaired perceptual integration. Those deficits could induce and increase the prominent symptoms of schizophrenia like impaired speech processing.

Acquired word deafness, and the temporal grain of sound representation in the primary auditory cortex.

PubMed

Phillips, D P; Farmer, M E

1990-11-15

This paper explores the nature of the processing disorder which underlies the speech discrimination deficit in the syndrome of acquired word deafness following from pathology to the primary auditory cortex. A critical examination of the evidence on this disorder revealed the following. First, the most profound forms of the condition are expressed not only in an isolation of the cerebral linguistic processor from auditory input, but in a failure of even the perceptual elaboration of the relevant sounds. Second, in agreement with earlier studies, we conclude that the perceptual dimension disturbed in word deafness is a temporal one. We argue, however, that it is not a generalized disorder of auditory temporal processing, but one which is largely restricted to the processing of sounds with temporal content in the milliseconds to tens-of-milliseconds time frame. The perceptual elaboration of sounds with temporal content outside that range, in either direction, may survive the disorder. Third, we present neurophysiological evidence that the primary auditory cortex has a special role in the representation of auditory events in that time frame, but not in the representation of auditory events with temporal grains outside that range.

Population responses in primary auditory cortex simultaneously represent the temporal envelope and periodicity features in natural speech.

PubMed

Abrams, Daniel A; Nicol, Trent; White-Schwoch, Travis; Zecker, Steven; Kraus, Nina

2017-05-01

Speech perception relies on a listener's ability to simultaneously resolve multiple temporal features in the speech signal. Little is known regarding neural mechanisms that enable the simultaneous coding of concurrent temporal features in speech. Here we show that two categories of temporal features in speech, the low-frequency speech envelope and periodicity cues, are processed by distinct neural mechanisms within the same population of cortical neurons. We measured population activity in primary auditory cortex of anesthetized guinea pig in response to three variants of a naturally produced sentence. Results show that the envelope of population responses closely tracks the speech envelope, and this cortical activity more closely reflects wider bandwidths of the speech envelope compared to narrow bands. Additionally, neuronal populations represent the fundamental frequency of speech robustly with phase-locked responses. Importantly, these two temporal features of speech are simultaneously observed within neuronal ensembles in auditory cortex in response to clear, conversation, and compressed speech exemplars. Results show that auditory cortical neurons are adept at simultaneously resolving multiple temporal features in extended speech sentences using discrete coding mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind Network.

PubMed

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Schütz, Claudia; Romanczuk-Seiferth, Nina; Grimm, Oliver; Haddad, Leila; Pöhland, Lydia; Garbusow, Maria; Schmitgen, Mike M; Kirsch, Peter; Esslinger, Christine; Rietschel, Marcella; Witt, Stephanie H; Nöthen, Markus M; Cichon, Sven; Mattheisen, Manuel; Mühleisen, Thomas; Jensen, Jimmy; Schott, Björn H; Maier, Wolfgang; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2014-04-01

The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal-temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network.

Gene x Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

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

Alia-Klein, N.; Alia-Klein, N.; Parvaz, M.A.

Long-term cocaine use has been associated with structural deficits in brain regions having dopamine-receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. The objective is to examine variations in gray matter volume (GMV) as a function of lifetime drug use and the genotype of the monoamine oxidase A gene, MAOA, in men with cocaine use disorders (CUD) and healthy male controls. Forty individuals with CUD and 42 controls who underwent magnetic resonance imaging to assess GMV and were genotyped for the MAOA polymorphism (categorized as high- and low-repeat alleles).more » The impact of cocaine addiction on GMV, tested by (1) comparing the CUD group with controls, (2) testing diagnosis x MAOA interactions, and (3) correlating GMV with lifetime cocaine, alcohol, and cigarette smoking, and testing their unique contribution to GMV beyond other factors. The results are: (1) Individuals with CUD had reductions in GMV in the orbitofrontal, dorsolateral prefrontal, and temporal cortex and the hippocampus compared with controls; (2) The orbitofrontal cortex reductions were uniquely driven by CUD with low- MAOA genotype and by lifetime cocaine use; and (3) The GMV in the dorsolateral prefrontal cortex and hippocampus was driven by lifetime alcohol use beyond the genotype and other pertinent variables. Long-term cocaine users with the low-repeat MAOA allele have enhanced sensitivity to gray matter loss, specifically in the orbitofrontal cortex, indicating that this genotype may exacerbate the deleterious effects of cocaine in the brain. In addition, long-term alcohol use is a major contributor to gray matter loss in the dorsolateral prefrontal cortex and hippocampus, and is likely to further impair executive function and learning in cocaine addiction.« less

Further Evidence for the Impact of a Genome-Wide-Supported Psychosis Risk Variant in ZNF804A on the Theory of Mind Network

PubMed Central

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Schütz, Claudia; Romanczuk-Seiferth, Nina; Grimm, Oliver; Haddad, Leila; Pöhland, Lydia; Garbusow, Maria; Schmitgen, Mike M; Kirsch, Peter; Esslinger, Christine; Rietschel, Marcella; Witt, Stephanie H; Nöthen, Markus M; Cichon, Sven; Mattheisen, Manuel; Mühleisen, Thomas; Jensen, Jimmy; Schott, Björn H; Maier, Wolfgang; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2014-01-01

The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal–temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network. PMID:24247043

Role of motor cortex NMDA receptors in learning-dependent synaptic plasticity of behaving mice

PubMed Central

Hasan, Mazahir T.; Hernández-González, Samuel; Dogbevia, Godwin; Treviño, Mario; Bertocchi, Ilaria; Gruart, Agnès; Delgado-García, José M.

2013-01-01

The primary motor cortex has an important role in the precise execution of learned motor responses. During motor learning, synaptic efficacy between sensory and primary motor cortical neurons is enhanced, possibly involving long-term potentiation and N-methyl-D-aspartate (NMDA)-specific glutamate receptor function. To investigate whether NMDA receptor in the primary motor cortex can act as a coincidence detector for activity-dependent changes in synaptic strength and associative learning, here we generate mice with deletion of the Grin1 gene, encoding the essential NMDA receptor subunit 1 (GluN1), specifically in the primary motor cortex. The loss of NMDA receptor function impairs primary motor cortex long-term potentiation in vivo. Importantly, it impairs the synaptic efficacy between the primary somatosensory and primary motor cortices and significantly reduces classically conditioned eyeblink responses. Furthermore, compared with wild-type littermates, mice lacking primary motor cortex show slower learning in Skinner-box tasks. Thus, primary motor cortex NMDA receptors are necessary for activity-dependent synaptic strengthening and associative learning. PMID:23978820

Impaired cortical activation in autistic children: is the mirror neuron system involved?

PubMed

Martineau, Joëlle; Cochin, Stéphanie; Magne, Rémy; Barthelemy, Catherine

2008-04-01

The inability to imitate becomes obvious early in autistic children and seems to contribute to learning delay and to disorders of communication and contact. Posture, motility and imitation disorders in autistic syndrome might be the consequence of an abnormality of sensori-motor integration, related to the visual perception of movement, and could reflect impairment of the mirror neuron system (MNS). We compared EEG activity during the observation of videos showing actions or still scenes in 14 right-handed autistic children and 14 right-handed, age- and gender-matched control children (3 girls and 11 boys, aged 5 years 3 months-7 years 11 months). We showed desynchronisation of the EEG in the motor cerebral cortex and the frontal and temporal areas during observation of human actions in the group of healthy children. No such desynchronisation was found in autistic children. Moreover, inversion of the pattern of hemispheric activation was found in autistic children, with increased cortical activity in the right hemisphere in the posterior region, including the centro-parietal and temporo-occipital sites. These results are in agreement with the hypothesis of impairment of the mirror neuron system in autistic disorder.

Temporal coordination of olfactory cortex sharp-wave activity with up- and downstates in the orbitofrontal cortex during slow-wave sleep.

PubMed

Onisawa, Naomi; Manabe, Hiroyuki; Mori, Kensaku

2017-01-01

During slow-wave sleep, interareal communications via coordinated, slow oscillatory activities occur in the large-scale networks of the mammalian neocortex. Because olfactory cortex (OC) areas, which belong to paleocortex, show characteristic sharp-wave (SPW) activity during slow-wave sleep, we examined whether OC SPWs in freely behaving rats occur in temporal coordination with up- and downstates of the orbitofrontal cortex (OFC) slow oscillation. Simultaneous recordings of local field potentials and spike activities in the OC and OFC showed that during the downstate in the OFC, the OC also exhibited downstate with greatly reduced neuronal activity and suppression of SPW generation. OC SPWs occurred during two distinct phases of the upstate of the OFC: early-phase SPWs occurred at the start of upstate shortly after the down-to-up transition in the OFC, whereas late-phase SPWs were generated at the end of upstate shortly before the up-to-down transition. Such temporal coordination between neocortical up- and downstates and olfactory system SPWs was observed between the prefrontal cortex areas (OFC and medial prefrontal cortex) and the OC areas (anterior piriform cortex and posterior piriform cortex). These results suggest that during slow-wave sleep, OC and OFC areas communicate preferentially in specific time windows shortly after the down-to-up transition and shortly before the up-to-down transition. Simultaneous recordings of local field potentials and spike activities in the anterior piriform cortex (APC) and orbitofrontal cortex (OFC) during slow-wave sleep showed that APC sharp waves tended to occur during two distinct phases of OFC upstate: early phase, shortly after the down-to-up transition, and late phase, shortly before the up-to-down transition, suggesting that during slow-wave sleep, olfactory cortex and OFC areas communicate preferentially in the specific time windows. Copyright © 2017 the American Physiological Society.

Temporal coordination of olfactory cortex sharp-wave activity with up- and downstates in the orbitofrontal cortex during slow-wave sleep

PubMed Central

Onisawa, Naomi; Mori, Kensaku

2016-01-01

During slow-wave sleep, interareal communications via coordinated, slow oscillatory activities occur in the large-scale networks of the mammalian neocortex. Because olfactory cortex (OC) areas, which belong to paleocortex, show characteristic sharp-wave (SPW) activity during slow-wave sleep, we examined whether OC SPWs in freely behaving rats occur in temporal coordination with up- and downstates of the orbitofrontal cortex (OFC) slow oscillation. Simultaneous recordings of local field potentials and spike activities in the OC and OFC showed that during the downstate in the OFC, the OC also exhibited downstate with greatly reduced neuronal activity and suppression of SPW generation. OC SPWs occurred during two distinct phases of the upstate of the OFC: early-phase SPWs occurred at the start of upstate shortly after the down-to-up transition in the OFC, whereas late-phase SPWs were generated at the end of upstate shortly before the up-to-down transition. Such temporal coordination between neocortical up- and downstates and olfactory system SPWs was observed between the prefrontal cortex areas (OFC and medial prefrontal cortex) and the OC areas (anterior piriform cortex and posterior piriform cortex). These results suggest that during slow-wave sleep, OC and OFC areas communicate preferentially in specific time windows shortly after the down-to-up transition and shortly before the up-to-down transition. NEW & NOTEWORTHY Simultaneous recordings of local field potentials and spike activities in the anterior piriform cortex (APC) and orbitofrontal cortex (OFC) during slow-wave sleep showed that APC sharp waves tended to occur during two distinct phases of OFC upstate: early phase, shortly after the down-to-up transition, and late phase, shortly before the up-to-down transition, suggesting that during slow-wave sleep, olfactory cortex and OFC areas communicate preferentially in the specific time windows. PMID:27733591

Spatio-temporal distribution of brain activity associated with audio-visually congruent and incongruent speech and the McGurk Effect.

PubMed

Pratt, Hillel; Bleich, Naomi; Mittelman, Nomi

2015-11-01

Spatio-temporal distributions of cortical activity to audio-visual presentations of meaningless vowel-consonant-vowels and the effects of audio-visual congruence/incongruence, with emphasis on the McGurk effect, were studied. The McGurk effect occurs when a clearly audible syllable with one consonant, is presented simultaneously with a visual presentation of a face articulating a syllable with a different consonant and the resulting percept is a syllable with a consonant other than the auditorily presented one. Twenty subjects listened to pairs of audio-visually congruent or incongruent utterances and indicated whether pair members were the same or not. Source current densities of event-related potentials to the first utterance in the pair were estimated and effects of stimulus-response combinations, brain area, hemisphere, and clarity of visual articulation were assessed. Auditory cortex, superior parietal cortex, and middle temporal cortex were the most consistently involved areas across experimental conditions. Early (<200 msec) processing of the consonant was overall prominent in the left hemisphere, except right hemisphere prominence in superior parietal cortex and secondary visual cortex. Clarity of visual articulation impacted activity in secondary visual cortex and Wernicke's area. McGurk perception was associated with decreased activity in primary and secondary auditory cortices and Wernicke's area before 100 msec, increased activity around 100 msec which decreased again around 180 msec. Activity in Broca's area was unaffected by McGurk perception and was only increased to congruent audio-visual stimuli 30-70 msec following consonant onset. The results suggest left hemisphere prominence in the effects of stimulus and response conditions on eight brain areas involved in dynamically distributed parallel processing of audio-visual integration. Initially (30-70 msec) subcortical contributions to auditory cortex, superior parietal cortex, and middle temporal cortex occur. During 100-140 msec, peristriate visual influences and Wernicke's area join in the processing. Resolution of incongruent audio-visual inputs is then attempted, and if successful, McGurk perception occurs and cortical activity in left hemisphere further increases between 170 and 260 msec.

Motor signatures of emotional reactivity in frontotemporal dementia.

PubMed

Marshall, Charles R; Hardy, Chris J D; Russell, Lucy L; Clark, Camilla N; Bond, Rebecca L; Dick, Katrina M; Brotherhood, Emilie V; Mummery, Cath J; Schott, Jonathan M; Rohrer, Jonathan D; Kilner, James M; Warren, Jason D

2018-01-18

Automatic motor mimicry is essential to the normal processing of perceived emotion, and disrupted automatic imitation might underpin socio-emotional deficits in neurodegenerative diseases, particularly the frontotemporal dementias. However, the pathophysiology of emotional reactivity in these diseases has not been elucidated. We studied facial electromyographic responses during emotion identification on viewing videos of dynamic facial expressions in 37 patients representing canonical frontotemporal dementia syndromes versus 21 healthy older individuals. Neuroanatomical associations of emotional expression identification accuracy and facial muscle reactivity were assessed using voxel-based morphometry. Controls showed characteristic profiles of automatic imitation, and this response predicted correct emotion identification. Automatic imitation was reduced in the behavioural and right temporal variant groups, while the normal coupling between imitation and correct identification was lost in the right temporal and semantic variant groups. Grey matter correlates of emotion identification and imitation were delineated within a distributed network including primary visual and motor, prefrontal, insular, anterior temporal and temporo-occipital junctional areas, with common involvement of supplementary motor cortex across syndromes. Impaired emotional mimesis may be a core mechanism of disordered emotional signal understanding and reactivity in frontotemporal dementia, with implications for the development of novel physiological biomarkers of socio-emotional dysfunction in these diseases.

Similarities and differences between parietal and frontal patients in autobiographical and constructed experience tasks

PubMed Central

Berryhill, Marian E.; Picasso, Lauren; Arnold, Robert; Drowos, David; Olson, Ingrid R.

2010-01-01

Recent findings suggest that constructed experience, the ability to envision future events, activates the same cortical network as recollection of past events. For example, damage to one key area, the hippocampus, impairs patients' ability to remember the past and to imagine novel experiences (Hassabis, Kumaran, Vann & Maguire, 2007). Here, we investigated whether damage to two other areas, posterior parietal cortex and prefrontal cortex, also impairs this ability. Patients with bilateral posterior parietal lesions or unilateral prefrontal lesions were tested in their ability to describe imaginary future events. Only parietal patients were impaired at freely describing autobiographical memories, but both patient groups were impaired when elaborating constructed experiences. This dissociation suggests that parietal and prefrontal structures are differentially involved in constructed experience. Current tasks may impose overly broad cognitive demands making it impossible to specify the deficient cognitive component in any patient group. These findings provide additional constraints regarding the mechanistic role of the parietal cortex in memory. PMID:20096710

Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa

PubMed Central

Brooks, Samantha J.; O′Daly, Owen G.; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C. R.; Schiöth, Helgi B.; Treasure, Janet; Campbell, Iain C.

2011-01-01

Background Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating. PMID:21799807

Effects of BDNF Val66Met polymorphism on brain metabolism in Alzheimer's disease.

PubMed

Xu, Cunlu; Wang, Zhenhua; Fan, Ming; Liu, Bing; Song, Ming; Zhen, Xiantong; Jiang, Tianzi

2010-08-23

Earlier studies showed that the Val66Met polymorphisms of the brain-derived neurotrophic factor differentially affect gray matter volume and brain region activities. This study used resting positron emission tomography to investigate the relationship between the polymorphisms of Val66Met and the regional cerebral metabolic rate in the brain. We analyzed the positron emission tomography images of 215 patients from the Alzheimer's Disease Neuroimaging Initiative and found significant differences in the parahippocampal gyrus, superior temporal gyrus, prefrontal cortex, and inferior parietal lobule when comparing Met carriers with noncarriers among both the normal controls and those with mild cognitive impairment. For those with Alzheimer's disease, we also found additional differences in the bilateral insula between the carriers and noncarriers.

A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control.

PubMed

Tolomeo, Serenella; Christmas, David; Jentzsch, Ines; Johnston, Blair; Sprengelmeyer, Reiner; Matthews, Keith; Douglas Steele, J

2016-06-01

Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. It has previously been proposed that this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral anterior cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy control subjects. Using the Ekman 60 faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received anterior cingulotomy were impaired in recognizing negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with this hypothesis, we found that larger volume lesions predicted more impairment in recognizing fear, disgust and anger, and no impairment in recognizing facial expressions of surprise or happiness. However, we found no impairment in recognizing expressions of sadness. Also consistent with the hypothesis, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman's meta-analysis-derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimizing behaviour in the presence of such stimuli, our findings support the assertion that this region has a causal role in these processes. While the clinical justification for cingulotomy is empirical and not theoretical, it is plausible that lesions within a brain region associated with the subjective experience of negative affect and pain may be therapeutic for patients with otherwise intractable mood, anxiety and pain syndromes. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Perseverative Interference with Object-in-Place Scene Learning in Rhesus Monkeys with Bilateral Ablation of Ventrolateral Prefrontal Cortex

ERIC Educational Resources Information Center

Baxter, Mark G.; Browning, Philip G. F.; Mitchell, Anna S.

2008-01-01

Surgical disconnection of the frontal cortex and inferotemporal cortex severely impairs many aspects of visual learning and memory, including learning of new object-in-place scene memory problems, a monkey model of episodic memory. As part of a study of specialization within prefrontal cortex in visual learning and memory, we tested monkeys with…

Interactions between visual and semantic processing during object recognition revealed by modulatory effects of age of acquisition.

PubMed

Urooj, Uzma; Cornelissen, Piers L; Simpson, Michael I G; Wheat, Katherine L; Woods, Will; Barca, Laura; Ellis, Andrew W

2014-02-15

The age of acquisition (AoA) of objects and their names is a powerful determinant of processing speed in adulthood, with early-acquired objects being recognized and named faster than late-acquired objects. Previous research using fMRI (Ellis et al., 2006. Traces of vocabulary acquisition in the brain: evidence from covert object naming. NeuroImage 33, 958-968) found that AoA modulated the strength of BOLD responses in both occipital and left anterior temporal cortex during object naming. We used magnetoencephalography (MEG) to explore in more detail the nature of the influence of AoA on activity in those two regions. Covert object naming recruited a network within the left hemisphere that is familiar from previous research, including visual, left occipito-temporal, anterior temporal and inferior frontal regions. Region of interest (ROI) analyses found that occipital cortex generated a rapid evoked response (~75-200 ms at 0-40 Hz) that peaked at 95 ms but was not modulated by AoA. That response was followed by a complex of later occipital responses that extended from ~300 to 850 ms and were stronger to early- than late-acquired items from ~325 to 675 ms at 10-20 Hz in the induced rather than the evoked component. Left anterior temporal cortex showed an evoked response that occurred significantly later than the first occipital response (~100-400 ms at 0-10 Hz with a peak at 191 ms) and was stronger to early- than late-acquired items from ~100 to 300 ms at 2-12 Hz. A later anterior temporal response from ~550 to 1050 ms at 5-20 Hz was not modulated by AoA. The results indicate that the initial analysis of object forms in visual cortex is not influenced by AoA. A fastforward sweep of activation from occipital and left anterior temporal cortex then results in stronger activation of semantic representations for early- than late-acquired objects. Top-down re-activation of occipital cortex by semantic representations is then greater for early than late acquired objects resulting in delayed modulation of the visual response. Copyright © 2013 Elsevier Inc. All rights reserved.

Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis.

PubMed

Meier, Sandra L; Charleston, Alison J; Tippett, Lynette J

2010-11-01

Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis without dementia, some with no signs of dysfunction in tasks sensitive to other regions of prefrontal cortex. This demonstration of variability in cognitive integrity supports previous research indicating amyotrophic lateral sclerosis is a heterogeneous disease.

Subthalamic Nucleus Stimulation Modulates Motor Cortex Oscillatory Activity in Parkinson's Disease

ERIC Educational Resources Information Center

Devos, D.; Labyt, E.; Derambure, P.; Bourriez, J. L.; Cassim, F.; Reyns, N.; Blond, S.; Guieu, J. D.; Destee, A.; Defebvre, L.

2004-01-01

In Parkinson's disease, impaired motor preparation has been related to an increased latency in the appearance of movement-related desynchronization (MRD) throughout the contralateral primary sensorimotor (PSM) cortex. Internal globus pallidus (GPi) stimulation improved movement desynchronization over the PSM cortex during movement execution but…

Lesions to polar/orbital prefrontal cortex selectively impair reasoning about emotional material.

PubMed

Goel, Vinod; Lam, Elaine; Smith, Kathleen W; Goel, Amit; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

2017-05-01

While it is widely accepted that lesions to orbital prefrontal cortex lead to emotion related disruptions and poor decision-making, there is very little patient data on this issue involving actual logical reasoning tasks. We tested patients with circumscribed, focal lesions largely confined to polar/orbital prefrontal cortex (BA 10 & 11) (N=17) on logical reasoning tasks involving neutral and emotional content, and compared their performance to that of an age and education-matched normal control group (N=22) and a posterior lesion control group (N=24). Our results revealed a significant group by content interaction driven by a selective impairment in the polar/orbital prefrontal cortex group compared to healthy normal controls and to the parietal patient group, in the emotional content reasoning trials. Subsequent analyses of congruent and incongruent reasoning trials indicated that this impairment was driven by the poor performance of patients with polar/orbital lesions in the incongruent trials. We conclude that the polar/orbital prefrontal cortex plays a critical role in filtering emotionally charged content from the material before it is passed on to the reasoning system in lateral/dorsal regions of prefrontal cortex. Where unfiltered content is passed to the reasoning engine, either as a result of pathology (as in the case of our patients) or as a result of individual differences, reasoning performance suffers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lesions to Polar/Orbital Prefrontal Cortex Selectively Impair Reasoning about Emotional Material

PubMed Central

Goel, Vinod; Lam, Elaine; Smith, Kathleen W.; Goel, Amit; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

2017-01-01

While it is widely accepted that lesions to orbital prefrontal cortex lead to emotion related disruptions and poor decision-making, there is very little patient data on this issue involving actual logical reasoning tasks. We tested patients with circumscribed, focal lesions largely confined to polar/orbital prefrontal cortex (BA 10 & 11) (N=17) on logical reasoning tasks involving neutral and emotional content, and compared their performance to that of an age and education-matched normal control group (N=22) and a posterior lesion control group (N=24). Our results revealed a significant group by content interaction driven by a selective impairment in the polar/orbital prefrontal cortex group compared to healthy normal controls and to the parietal patient group, in the emotional content reasoning trials. Subsequent analyses of congruent and incongruent reasoning trials indicated that this impairment was driven by the poor performance of patients with polar/orbital lesions in the incongruent trials. We conclude that the polar/orbital prefrontal cortex plays a critical role in filtering emotionally charged content from the material before it is passed on to the reasoning system in lateral/dorsal regions of prefrontal cortex. Where unfiltered content is passed to the reasoning engine, either as a result of pathology (as in the case of our patients) or as a result of individual differences, reasoning performance suffers. PMID:28263798

Evidence of degraded representation of speech in noise, in the aging midbrain and cortex

PubMed Central

Simon, Jonathan Z.; Anderson, Samira

2016-01-01

Humans have a remarkable ability to track and understand speech in unfavorable conditions, such as in background noise, but speech understanding in noise does deteriorate with age. Results from several studies have shown that in younger adults, low-frequency auditory cortical activity reliably synchronizes to the speech envelope, even when the background noise is considerably louder than the speech signal. However, cortical speech processing may be limited by age-related decreases in the precision of neural synchronization in the midbrain. To understand better the neural mechanisms contributing to impaired speech perception in older adults, we investigated how aging affects midbrain and cortical encoding of speech when presented in quiet and in the presence of a single-competing talker. Our results suggest that central auditory temporal processing deficits in older adults manifest in both the midbrain and in the cortex. Specifically, midbrain frequency following responses to a speech syllable are more degraded in noise in older adults than in younger adults. This suggests a failure of the midbrain auditory mechanisms needed to compensate for the presence of a competing talker. Similarly, in cortical responses, older adults show larger reductions than younger adults in their ability to encode the speech envelope when a competing talker is added. Interestingly, older adults showed an exaggerated cortical representation of speech in both quiet and noise conditions, suggesting a possible imbalance between inhibitory and excitatory processes, or diminished network connectivity that may impair their ability to encode speech efficiently. PMID:27535374

Orbital prefrontal cortex is required for object-in-place scene memory but not performance of a strategy implementation task.

PubMed

Baxter, Mark G; Gaffan, David; Kyriazis, Diana A; Mitchell, Anna S

2007-10-17

The orbital prefrontal cortex is thought to be involved in behavioral flexibility in primates, and human neuroimaging studies have identified orbital prefrontal activation during episodic memory encoding. The goal of the present study was to ascertain whether deficits in strategy implementation and episodic memory that occur after ablation of the entire prefrontal cortex can be ascribed to damage to the orbital prefrontal cortex. Rhesus monkeys were preoperatively trained on two behavioral tasks, the performance of both of which is severely impaired by the disconnection of frontal cortex from inferotemporal cortex. In the strategy implementation task, monkeys were required to learn about two categories of objects, each associated with a different strategy that had to be performed to obtain food reward. The different strategies had to be applied flexibly to optimize the rate of reward delivery. In the scene memory task, monkeys learned 20 new object-in-place discrimination problems in each session. Monkeys were tested on both tasks before and after bilateral ablation of orbital prefrontal cortex. These lesions impaired new scene learning but had no effect on strategy implementation. This finding supports a role for the orbital prefrontal cortex in memory but places limits on the involvement of orbital prefrontal cortex in the representation and implementation of behavioral goals and strategies.

The frequency modulated auditory evoked response (FMAER), a technical advance for study of childhood language disorders: cortical source localization and selected case studies

PubMed Central

2013-01-01

Background Language comprehension requires decoding of complex, rapidly changing speech streams. Detecting changes of frequency modulation (FM) within speech is hypothesized as essential for accurate phoneme detection, and thus, for spoken word comprehension. Despite past demonstration of FM auditory evoked response (FMAER) utility in language disorder investigations, it is seldom utilized clinically. This report's purpose is to facilitate clinical use by explaining analytic pitfalls, demonstrating sites of cortical origin, and illustrating potential utility. Results FMAERs collected from children with language disorders, including Developmental Dysphasia, Landau-Kleffner syndrome (LKS), and autism spectrum disorder (ASD) and also normal controls - utilizing multi-channel reference-free recordings assisted by discrete source analysis - provided demonstratrions of cortical origin and examples of clinical utility. Recordings from inpatient epileptics with indwelling cortical electrodes provided direct assessment of FMAER origin. The FMAER is shown to normally arise from bilateral posterior superior temporal gyri and immediate temporal lobe surround. Childhood language disorders associated with prominent receptive deficits demonstrate absent left or bilateral FMAER temporal lobe responses. When receptive language is spared, the FMAER may remain present bilaterally. Analyses based upon mastoid or ear reference electrodes are shown to result in erroneous conclusions. Serial FMAER studies may dynamically track status of underlying language processing in LKS. FMAERs in ASD with language impairment may be normal or abnormal. Cortical FMAERs can locate language cortex when conventional cortical stimulation does not. Conclusion The FMAER measures the processing by the superior temporal gyri and adjacent cortex of rapid frequency modulation within an auditory stream. Clinical disorders associated with receptive deficits are shown to demonstrate absent left or bilateral responses. Serial FMAERs may be useful for tracking language change in LKS. Cortical FMAERs may augment invasive cortical language testing in epilepsy surgical patients. The FMAER may be normal in ASD and other language disorders when pathology spares the superior temporal gyrus and surround but presumably involves other brain regions. Ear/mastoid reference electrodes should be avoided and multichannel, reference free recordings utilized. Source analysis may assist in better understanding of complex FMAER findings. PMID:23351174

Sex differences in cortical thickness and their possible genetic and sex hormonal underpinnings.

PubMed

Savic, I; Arver, S

2014-12-01

Although it has been shown that cortical thickness (Cth) differs between sexes, the underlying mechanisms are unknown. Seeing as XXY males have 1 extra X chromosome, we investigated the possible effects of X- and sex-chromosome dosage on Cth by comparing data from 31 XXY males with 39 XY and 47 XX controls. Plasma testosterone and estrogen were also measured in an effort to differentiate between possible sex-hormone and sex-chromosome gene effects. Cth was calculated with FreeSurfer software. Parietal and occipital Cth was greater in XX females than XY males. In these regions Cth was inversely correlated with z-normalized testosterone. In the motor strip, the cortex was thinner in XY males compared with both XX females and XXY males, indicating the possibility of an X-chromosome gene-dosage effect. XXY males had thinner right superior temporal and left middle temporal cortex, and a thicker right orbitofrontal cortex and lingual cortex than both control groups. Based on these data and previous reports from women with XO monosomy, it is hypothesized that programming of the motor cortex is influenced by processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of the superior temporal cortex is mediated by X-chromosome escapee genes with Y-homologs. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Multi-template analysis of human perirhinal cortex in brain MRI: Explicitly accounting for anatomical variability

PubMed Central

Xie, Long; Pluta, John B.; Das, Sandhitsu R.; Wisse, Laura E.M.; Wang, Hongzhi; Mancuso, Lauren; Kliot, Dasha; Avants, Brian B.; Ding, Song-Lin; Manjón, José V.; Wolk, David A.; Yushkevich, Paul A.

2016-01-01

Rational The human perirhinal cortex (PRC) plays critical roles in episodic and semantic memory and visual perception. The PRC consists of Brodmann areas 35 and 36 (BA35, BA36). In Alzheimer's disease (AD), BA35 is the first cortical site affected by neurofibrillary tangle pathology, which is closely linked to neural injury in AD. Large anatomical variability, manifested in the form of different cortical folding and branching patterns, makes it difficult to segment the PRC in MRI scans. Pathology studies have found that in ~97% of specimens, the PRC falls into one of three discrete anatomical variants. However, current methods for PRC segmentation and morphometry in MRI are based on single-template approaches, which may not be able to accurately model these discrete variants Methods A multi-template analysis pipeline that explicitly accounts for anatomical variability is used to automatically label the PRC and measure its thickness in T2-weighted MRI scans. The pipeline uses multi-atlas segmentation to automatically label medial temporal lobe cortices including entorhinal cortex, PRC and the parahippocampal cortex. Pairwise registration between label maps and clustering based on residual dissimilarity after registration are used to construct separate templates for the anatomical variants of the PRC. An optimal path of deformations linking these templates is used to establish correspondences between all the subjects. Experimental evaluation focuses on the ability of single-template and multi-template analyses to detect differences in the thickness of medial temporal lobe cortices between patients with amnestic mild cognitive impairment (aMCI, n=41) and age-matched controls (n=44). Results The proposed technique is able to generate templates that recover the three dominant discrete variants of PRC and establish more meaningful correspondences between subjects than a single-template approach. The largest reduction in thickness associated with aMCI, in absolute terms, was found in left BA35 using both regional and summary thickness measures. Further, statistical maps of regional thickness difference between aMCI and controls revealed different patterns for the three anatomical variants. PMID:27702610

Emotional decision-making and its dissociable components in schizophrenia and schizoaffective disorder: a behavioural and MRI investigation.

PubMed

Premkumar, Preethi; Fannon, Dominic; Kuipers, Elizabeth; Simmons, Andrew; Frangou, Sophia; Kumari, Veena

2008-01-01

Cognitive decision-making is known to be deficient, but relatively less is known about emotional decision-making in schizophrenia. The Iowa gambling task (IGT) is considered a reliable probe of emotional decision-making and believed to reflect orbitofrontal cortex (OFC) function. The expectancy-valence model of IGT performance implicates three dissociable components, namely, attention to reward, memory for past, relative to recent, outcomes and impulsivity in emotional decision-making. We examined IGT performance, its three components, and their grey matter volume (GMV) correlates in 75 stable patients with schizophrenia, relative to 25 healthy individuals. Patients, relative to controls, showed impaired IGT performance and poor memory for past, relative to recent, outcomes. IGT performance correlated with GMV in the OFC in controls, but not patients. There were associations between (a) attention to reward and GMV in the frontal, temporal, parietal and striatal regions in controls, and in the temporal and thalamic regions in patients, (b) memory for past outcomes and GMV in the temporal region in controls, and the frontal and temporal regions in patients, and (c) low impulsivity and greater GMV in the frontal, temporal, posterior cingulate and occipital regions in controls, and in the frontal, temporal and posterior cingulate regions in patients. Most IGT-GMV associations were stronger in controls. It is concluded that (i) poor memory, rather than less attention to reward or impulsivity, contributes to IGT performance deficit, and (ii) the relationship of IGT performance and its components with GMVs especially in the frontal and temporal lobes is lost or attenuated in schizophrenia.

Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease.

PubMed

Li, Chuanming; Wang, Jian; Gui, Li; Zheng, Jian; Liu, Chen; Du, Hanjian

2011-01-01

Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.

Protective effect of naringin on pentylenetetrazole (PTZ)-induced kindling; possible mechanisms of antikindling, memory improvement, and neuroprotection.

PubMed

Kola, Phani Kumar; Akula, Annapurna; NissankaraRao, Lakshmi Sudeepthi; Danduga, R Ch Sekhara Reddy

2017-10-01

The present study investigated the effects of Naringin on seizure severity, progress of kindling, memory impairment, oxidative stress, neurochemicals, and neural damage in Pentylenetetrazole (PTZ)-induced kindling. Alternate intra-peritoneal injections of PTZ induced kindling at 22 injections of PTZ. In comparison with the PTZ group, pretreatment with Naringin 30 min prior to PTZ administration and on a PTZ-free day was found to lead to a decreased seizure score, a mitigated progress of kindling, decreased transfer latency, and increased total number of arm entries, % alternation behavior in Y maze, and % conditioned avoidance response in a pole climbing apparatus. Biochemical analysis of the frontal and temporal cortexes and the hippocampus of the brain showed that Naringin attenuated the level of lipid peroxidation (MDA) and augmented the reduced glutathione, superoxide dismutase, catalase, and total thiol results in decreased oxidative stress compared with the PTZ group and control group. Investigation of neurochemicals revealed a minute change in gamma amino butyric acid (GABA), glutamate and dopamine, and decreased AChE in the three regions. Increased CA1 neuronal density in the hippocampus and increased cell density in the frontal and temporal regions indicate the potential of naringin to act against PTZ-induced kindling, memory impairment, oxidative stress, neurochemical changes, and histological aberrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between changes in rat behavior and integral biochemical indexes determined by laser correlation spectroscopy after photothrombosis of the prefrontal cortex.

PubMed

Romanova, G A; Shakova, F M; Kovaleva, O I; Pivovarov, V V; Khlebnikova, N N; Karganov, M Yu

2004-02-01

Experiments on rats showed that Noopept improved retention and retrieval of conditioned passive avoidance response after phototrombosis of the prefrontal cortex (a procedure impairing retention of memory traces). The impairment of mnesic functions was accompanied by changes in integral biochemical indexes of the plasma determined by laser correlation spectroscopy. Treatment of behavioral disorders with Noopepet normalized biochemical indexes.

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

PubMed

Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

2016-03-01

Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

Cortex-based inter-subject analysis of iEEG and fMRI data sets: application to sustained task-related BOLD and gamma responses.

PubMed

Esposito, Fabrizio; Singer, Neomi; Podlipsky, Ilana; Fried, Itzhak; Hendler, Talma; Goebel, Rainer

2013-02-01

Linking regional metabolic changes with fluctuations in the local electromagnetic fields directly on the surface of the human cerebral cortex is of tremendous importance for a better understanding of detailed brain processes. Functional magnetic resonance imaging (fMRI) and intra-cranial electro-encephalography (iEEG) measure two technically unrelated but spatially and temporally complementary sets of functional descriptions of human brain activity. In order to allow fine-grained spatio-temporal human brain mapping at the population-level, an effective comparative framework for the cortex-based inter-subject analysis of iEEG and fMRI data sets is needed. We combined fMRI and iEEG recordings of the same patients with epilepsy during alternated intervals of passive movie viewing and music listening to explore the degree of local spatial correspondence and temporal coupling between blood oxygen level dependent (BOLD) fMRI changes and iEEG spectral power modulations across the cortical surface after cortex-based inter-subject alignment. To this purpose, we applied a simple model of the iEEG activity spread around each electrode location and the cortex-based inter-subject alignment procedure to transform discrete iEEG measurements into cortically distributed group patterns by establishing a fine anatomic correspondence of many iEEG cortical sites across multiple subjects. Our results demonstrate the feasibility of a multi-modal inter-subject cortex-based distributed analysis for combining iEEG and fMRI data sets acquired from multiple subjects with the same experimental paradigm but with different iEEG electrode coverage. The proposed iEEG-fMRI framework allows for improved group statistics in a common anatomical space and preserves the dynamic link between the temporal features of the two modalities. Copyright © 2012 Elsevier Inc. All rights reserved.

Self-Organization of Spatio-Temporal Hierarchy via Learning of Dynamic Visual Image Patterns on Action Sequences

PubMed Central

Jung, Minju; Hwang, Jungsik; Tani, Jun

2015-01-01

It is well known that the visual cortex efficiently processes high-dimensional spatial information by using a hierarchical structure. Recently, computational models that were inspired by the spatial hierarchy of the visual cortex have shown remarkable performance in image recognition. Up to now, however, most biological and computational modeling studies have mainly focused on the spatial domain and do not discuss temporal domain processing of the visual cortex. Several studies on the visual cortex and other brain areas associated with motor control support that the brain also uses its hierarchical structure as a processing mechanism for temporal information. Based on the success of previous computational models using spatial hierarchy and temporal hierarchy observed in the brain, the current report introduces a novel neural network model for the recognition of dynamic visual image patterns based solely on the learning of exemplars. This model is characterized by the application of both spatial and temporal constraints on local neural activities, resulting in the self-organization of a spatio-temporal hierarchy necessary for the recognition of complex dynamic visual image patterns. The evaluation with the Weizmann dataset in recognition of a set of prototypical human movement patterns showed that the proposed model is significantly robust in recognizing dynamically occluded visual patterns compared to other baseline models. Furthermore, an evaluation test for the recognition of concatenated sequences of those prototypical movement patterns indicated that the model is endowed with a remarkable capability for the contextual recognition of long-range dynamic visual image patterns. PMID:26147887

Self-Organization of Spatio-Temporal Hierarchy via Learning of Dynamic Visual Image Patterns on Action Sequences.

PubMed

Jung, Minju; Hwang, Jungsik; Tani, Jun

2015-01-01

It is well known that the visual cortex efficiently processes high-dimensional spatial information by using a hierarchical structure. Recently, computational models that were inspired by the spatial hierarchy of the visual cortex have shown remarkable performance in image recognition. Up to now, however, most biological and computational modeling studies have mainly focused on the spatial domain and do not discuss temporal domain processing of the visual cortex. Several studies on the visual cortex and other brain areas associated with motor control support that the brain also uses its hierarchical structure as a processing mechanism for temporal information. Based on the success of previous computational models using spatial hierarchy and temporal hierarchy observed in the brain, the current report introduces a novel neural network model for the recognition of dynamic visual image patterns based solely on the learning of exemplars. This model is characterized by the application of both spatial and temporal constraints on local neural activities, resulting in the self-organization of a spatio-temporal hierarchy necessary for the recognition of complex dynamic visual image patterns. The evaluation with the Weizmann dataset in recognition of a set of prototypical human movement patterns showed that the proposed model is significantly robust in recognizing dynamically occluded visual patterns compared to other baseline models. Furthermore, an evaluation test for the recognition of concatenated sequences of those prototypical movement patterns indicated that the model is endowed with a remarkable capability for the contextual recognition of long-range dynamic visual image patterns.

Proton magnetic resonance spectroscopy (MRS) in on-line game addiction.

PubMed

Han, Doug Hyun; Lee, Young Sik; Shi, Xianfeng; Renshaw, Perry F

2014-11-01

Recent brain imaging studies suggested that both the frontal and temporal cortices are important candidate areas for mediating the symptoms of internet addiction. We hypothesized that deficits of prefrontal and temporal cortical function in patients with on-line game addiction (PGA) would be reflected in decreased levels of N-acetyl aspartate (NAA) and cytosolic, choline containing compound (Cho). Seventy three young PGA and 38 age and sex matched healthy control subjects were recruited in the study. Structural MR and (1)H MRS data were acquired using a 3.0 T MRI scanner. Voxels were sequentially placed in right frontal cortex and right medial temporal cortices. In the right frontal cortex, the levels of NAA in PGA were lower than those in healthy controls. In the medial temporal cortex, the levels of Cho in PGA participants were lower than those observed in healthy controls. The Young Internet Addiction Scale (YIAS) scores and perseverative responses in PGA were negatively correlated with the level of NAA in right frontal cortex. The Beck Depressive Inventory (BDI) scores in the PGA cohort were negatively correlated with Cho levels in the right temporal lobe. To the best of our knowledge, this is the first MRS study of individuals with on-line game addiction. Although, the subjects with on-line game addiction in the current study were free from psychiatric co-morbidity, patients with on-line game addiction appear to share characteristics with ADHD and MDD in terms of neurochemical changes in frontal and temporal cortices. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of the parahippocampal cortex in memory for the configuration but not the identity of objects: converging evidence from patients with selective thermal lesions and fMRI.

PubMed

Bohbot, Véronique D; Allen, John J B; Dagher, Alain; Dumoulin, Serge O; Evans, Alan C; Petrides, Michael; Kalina, Miroslav; Stepankova, Katerina; Nadel, Lynn

2015-01-01

The parahippocampal cortex and hippocampus are brain structures known to be involved in memory. However, the unique contribution of the parahippocampal cortex remains unclear. The current study investigates memory for object identity and memory of the configuration of objects in patients with small thermo-coagulation lesions to the hippocampus or the parahippocampal cortex. Results showed that in contrast to control participants and patients with damage to the hippocampus leaving the parahippocampal cortex intact, patients with lesions that included the right parahippocampal cortex (RPH) were severely impaired on a task that required learning the spatial configuration of objects on a computer screen; these patients, however, were not impaired at learning the identity of objects. Conversely, we found that patients with lesions to the right hippocampus (RH) or left hippocampus (LH), sparing the parahippocampal cortex, performed just as well as the control participants. Furthermore, they were not impaired on the object identity task. In the functional Magnetic Resonance Imaging (fMRI) experiment, healthy young adults performed the same tasks. Consistent with the findings of the lesion study, the fMRI results showed significant activity in the RPH in the memory for the spatial configuration condition, but not memory for object identity. Furthermore, the pattern of fMRI activity measured in the baseline control conditions decreased specifically in the parahippocampal cortex as a result of the experimental task, providing evidence for task specific repetition suppression. In summary, while our previous studies demonstrated that the hippocampus is critical to the construction of a cognitive map, both the lesion and fMRI studies have shown an involvement of the RPH for learning spatial configurations of objects but not object identity, and that this takes place independent of the hippocampus.

Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

PubMed

Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

2011-03-01

Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Convergent and divergent intranetwork and internetwork connectivity patterns in patients with remitted late-life depression and amnestic mild cognitive impairment.

PubMed

Chen, Jiu; Shu, Hao; Wang, Zan; Zhan, Yafeng; Liu, Duan; Liao, Wenxiang; Xu, Lin; Liu, Yong; Zhang, Zhijun

2016-10-01

Both remitted late-life depression (rLLD) and amnesiac mild cognitive impairment (aMCI) alter brain functions in specific regions of the brain. They are also disconnection syndromes that are associated with a high risk of developing Alzheimer's disease (AD). Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) was performed to define the shared and distinct aberrant patterns in intranetwork and internetwork connectivity between rLLD and aMCI and to determine how knowledge of these differences might contribute to our essential understanding of the altered sequences involved in functional systems both inside and outside of resting-state networks. We used rs-fcMRI to investigate in five functionally well-defined brain networks in two large cohorts of subjects at high risk for AD (55 rLLD and 87 aMCI) and 114 healthy controls (HC). A reduced degree of functional connectivity was observed in the bilateral inferior temporal cortex and supplemental motor area, and reduced correlations were observed within the sensory-motor network (SMN) and in the default mode network (DMN)-control network (CON) pair in the rLLD group than the HC group. The aMCI group showed only focal functional changes in regions of interest pairs, a trend toward increased correlations within the salience network and SMN, and a trend toward a reduced correlation in the DMN-CON pair. Furthermore, the rLLD group exhibited more severely altered functional connectivity than the aMCI group. Interestingly, these altered connectivities were associated with specific multi-domain cognitive and behavioral functions in both rLLD and aMCI. The degree of functional connectivity in the right primary auditory areas was negatively correlated with Hamilton Depression Scale scores in rLLD. Notably, altered connectivity between the right middle temporal cortex and the posterior cerebellum was negatively correlated with Mattis Dementia Rating Scale scores in both rLLD and aMCI. These results demonstrate that rLLD and aMCI may share convergent and divergent aberrant intranetwork and internetwork connectivity patterns as a potential continuous spectrum of the same disease. They further suggest that dysfunctions in the right specific temporal-cerebellum neural circuit may contribute to the similarities observed in rLLD and aMCI conversion to AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task

PubMed Central

Janitzky, Kathrin; Lippert, Michael T.; Engelhorn, Achim; Tegtmeier, Jennifer; Goldschmidt, Jürgen; Heinze, Hans-Jochen; Ohl, Frank W.

2015-01-01

The locus coeruleus (LC) is the sole source of noradrenergic projections to the cortex and essential for attention-dependent cognitive processes. In this study we used unilateral optogenetic silencing of the LC in an attentional set-shifting task (ASST) to evaluate the influence of the LC on prefrontal cortex-dependent functions in mice. We expressed the halorhodopsin eNpHR 3.0 to reversibly silence LC activity during task performance, and found that silencing selectively impaired learning of those parts of the ASST that most strongly rely on cognitive flexibility. In particular, extra-dimensional set-shifting (EDS) and reversal learning was impaired, suggesting an involvement of the medial prefrontal cortex (mPFC) and the orbitofrontal cortex. In contrast, those parts of the task that are less dependent on cognitive flexibility, i.e., compound discrimination (CD) and the intra-dimensional shifts (IDS) were not affected. Furthermore, attentional set formation was unaffected by LC silencing. Our results therefore suggest a modulatory influence of the LC on cognitive flexibility, mediated by different frontal networks. PMID:26582980

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function.

PubMed

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L; Rajah, M Natasha

2016-06-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of muscarinic blockade in perirhinal cortex during visual recognition

PubMed Central

Tang, Yi; Mishkin, Mortimer; Aigner, Thomas G.

1997-01-01

Stimulus recognition in monkeys is severely impaired by destruction or dysfunction of the perirhinal cortex and also by systemic administration of the cholinergic-muscarinic receptor blocker, scopolamine. These two effects are shown here to be linked: Stimulus recognition was found to be significantly impaired after bilateral microinjection of scopolamine directly into the perirhinal cortex, but not after equivalent injections into the laterally adjacent visual area TE or into the dentate gyrus of the overlying hippocampal formation. The results suggest that the formation of stimulus memories depends critically on cholinergic-muscarinic activation of the perirhinal area, providing a new clue to how stimulus representations are stored. PMID:9356507

Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

NASA Astrophysics Data System (ADS)

Birnbaum, S. G.; Yuan, P. X.; Wang, M.; Vijayraghavan, S.; Bloom, A. K.; Davis, D. J.; Gobeske, K. T.; Sweatt, J. D.; Manji, H. K.; Arnsten, A. F. T.

2004-10-01

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

Repeated microinjections into the medial prefrontal cortex (mPFC) impair extinction of conditioned place preference in mice.

PubMed

Groblewski, Peter A; Cunningham, Christopher L

2012-04-21

The medial prefrontal cortex (mPFC) is important for extinction of many behaviors including conditioned place preference (CPP). We examined the effects of intra-mPFC inactivation (with bupivacaine) on extinction of ethanol-induced CPP in mice. Injections of both bupivacaine and vehicle impaired extinction whereas no-surgery control mice extinguished normally. Consistent with recently reported effects of mPFC lesions, these data suggest that extinction was impaired by excessive mPFC damage induced by repeated intracranial infusions. Copyright © 2012 Elsevier B.V. All rights reserved.

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory.

PubMed

Birnbaum, S G; Yuan, P X; Wang, M; Vijayraghavan, S; Bloom, A K; Davis, D J; Gobeske, K T; Sweatt, J D; Manji, H K; Arnsten, A F T

2004-10-29

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

Examining the effect of psychopathic traits on gray matter volume in a community substance abuse sample.

PubMed

Cope, Lora M; Shane, Matthew S; Segall, Judith M; Nyalakanti, Prashanth K; Stevens, Michael C; Pearlson, Godfrey D; Calhoun, Vince D; Kiehl, Kent A

2012-11-30

Psychopathy is believed to be associated with brain abnormalities in both paralimbic (i.e., orbitofrontal cortex, insula, temporal pole, parahippocampal gyrus, posterior cingulate) and limbic (i.e., amygdala, hippocampus, anterior cingulate) regions. Recent structural imaging studies in both community and prison samples are beginning to support this view. Sixty-six participants, recruited from community corrections centers, were administered the Hare psychopathy checklist-revised (PCL-R), and underwent magnetic resonance imaging (MRI). Voxel-based morphometry was used to test the hypothesis that psychopathic traits would be associated with gray matter reductions in limbic and paralimbic regions. Effects of lifetime drug and alcohol use on gray matter volume were covaried. Psychopathic traits were negatively associated with gray matter volumes in right insula and right hippocampus. Additionally, psychopathic traits were positively associated with gray matter volumes in bilateral orbital frontal cortex and right anterior cingulate. Exploratory regression analyses indicated that gray matter volumes within right hippocampus and left orbital frontal cortex combined to explain 21.8% of the variance in psychopathy scores. These results support the notion that psychopathic traits are associated with abnormal limbic and paralimbic gray matter volume. Furthermore, gray matter increases in areas shown to be functionally impaired suggest that the structure-function relationship may be more nuanced than previously thought. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Right Frontotemporal Cortex Mediates the Relationship between Cognitive Insight and Subjective Quality of Life in Patients with Schizophrenia

PubMed Central

Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Ohtachi, Hiroaki; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

2018-01-01

Although prior studies identified a relationship between cognitive insight and subjective quality of life (QOL) in patients with schizophrenia, the brain regions mediating this relationship remain unknown. Recent studies have shown that the ventrolateral prefrontal cortex may be particularly important for cognitive insight in individuals with schizophrenia. Here, we examined whether frontotemporal function mediates the relationship between cognitive insight and QOL in 64 participants, including 32 patients with schizophrenia and 32 healthy controls. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS), while participants’ subjective QOL was assessed using the Medical Outcomes Study 36-item Short-form Health Survey. Frontotemporal function was evaluated during a verbal fluency task using multichannel near-infrared spectroscopy. Consistent with previous findings, we found that frontotemporal function was impaired in patients with schizophrenia. Interestingly, our data also revealed that the right ventrolateral PFC and the right anterior part of the temporal cortex significantly mediated the relationship between the self-reflectiveness (SR) subscale of the BCIS and subjective QOL. These findings suggest that cognitive insight, particularly SR, is associated with subjective QOL in patients with schizophrenia via right frontotemporal function. The findings of this study provide important insight into a QOL model of schizophrenia, which may guide the development of cost-effective interventions that target frontotemporal function in patients with schizophrenia. PMID:29456514

Right Frontotemporal Cortex Mediates the Relationship between Cognitive Insight and Subjective Quality of Life in Patients with Schizophrenia.

PubMed

Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Ohtachi, Hiroaki; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

2018-01-01

Although prior studies identified a relationship between cognitive insight and subjective quality of life (QOL) in patients with schizophrenia, the brain regions mediating this relationship remain unknown. Recent studies have shown that the ventrolateral prefrontal cortex may be particularly important for cognitive insight in individuals with schizophrenia. Here, we examined whether frontotemporal function mediates the relationship between cognitive insight and QOL in 64 participants, including 32 patients with schizophrenia and 32 healthy controls. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS), while participants' subjective QOL was assessed using the Medical Outcomes Study 36-item Short-form Health Survey. Frontotemporal function was evaluated during a verbal fluency task using multichannel near-infrared spectroscopy. Consistent with previous findings, we found that frontotemporal function was impaired in patients with schizophrenia. Interestingly, our data also revealed that the right ventrolateral PFC and the right anterior part of the temporal cortex significantly mediated the relationship between the self-reflectiveness (SR) subscale of the BCIS and subjective QOL. These findings suggest that cognitive insight, particularly SR, is associated with subjective QOL in patients with schizophrenia via right frontotemporal function. The findings of this study provide important insight into a QOL model of schizophrenia, which may guide the development of cost-effective interventions that target frontotemporal function in patients with schizophrenia.

Orbitofrontal cortex function and structure in depression.

PubMed

Drevets, Wayne C

2007-12-01

The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.

From attentional gating in macaque primary visual cortex to dyslexia in humans.

PubMed

Vidyasagar, T R

2001-01-01

Selective attention is an important aspect of brain function that we need in coping with the immense and constant barrage of sensory information. One model of attention (Feature Integration Theory) that suggests an early selection of spatial locations of objects via an attentional spotlight would also solve the 'binding problem' (that is how do different attributes of each object get correctly bound together?). Our experiments have demonstrated modulation of specific locations of interest at the level of the primary visual cortex both in visual discrimination and memory tasks, where the actual locations of the targets was also important in being able to perform the task. It is suggested that the feedback mediating the modulation arises from the posterior parietal cortex, which would also be consistent with its known role in attentional control. In primates, the magnocellular (M) and parvocellular (P) pathways are the two major streams of inputs from the retina, carrying distinctly different types of information and they remain fairly segregated in their projections to the primary visual cortex and further into the extra-striate regions. The P inputs go mainly into the ventral (temporal) stream, while the dorsal (parietal) stream is dominated by M inputs. A theory of attentional gating is proposed here where the M dominated dorsal stream gates the P inputs into the ventral stream. This framework is used to provide a neural explanation of the processes involved in reading and in learning to read. This scheme also explains how a magnocellular deficit could cause the common reading impairment, dyslexia.

Predicting the Location of Human Perirhinal Cortex, Brodmann's area 35, from MRI

PubMed Central

Augustinack, Jean C.; Huber, Kristen E.; Stevens, Allison A.; Roy, Michelle; Frosch, Matthew P.; van der Kouwe, André J.W.; Wald, Lawrence L.; Van Leemput, Koen; McKee, Ann; Fischl, Bruce

2012-01-01

The perirhinal cortex (Brodmann's area 35) is a multimodal area that is important for normal memory function. Specifically, perirhinal cortex is involved in detection of novel objects and manifests neurofibrillary tangles in Alzheimer's disease very early in disease progression. We scanned ex vivo brain hemispheres at standard resolution (1 mm × 1 mm × 1 mm) to construct pial/white matter surfaces in FreeSurfer and scanned again at high resolution (120 μm × 120 μm × 120 μm) to determine cortical architectural boundaries. After labeling perirhinal area 35 in the high resolution images, we mapped the high resolution labels to the surface models to localize area 35 in fourteen cases. We validated the area boundaries determined using histological Nissl staining. To test the accuracy of the probabilistic mapping, we measured the Hausdorff distance between the predicted and true labels and found that the median Hausdorff distance was 4.0 mm for left hemispheres (n = 7) and 3.2 mm for right hemispheres (n = 7) across subjects. To show the utility of perirhinal localization, we mapped our labels to a subset of the Alzheimer's Disease Neuroimaging Initiative dataset and found decreased cortical thickness measures in mild cognitive impairment and Alzheimer's disease compared to controls in the predicted perirhinal area 35. Our ex vivo probabilistic mapping of perirhinal cortex provides histologically validated, automated and accurate labeling of architectonic regions in the medial temporal lobe, and facilitates the analysis of atrophic changes in a large dataset for earlier detection and diagnosis. PMID:22960087

Production of verbs related to body movement in amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD).

PubMed

Cousins, Katheryn A Q; Ash, Sharon; Grossman, Murray

2018-03-01

Theories of grounded cognition propose that action verb knowledge relies in part on motor processing regions, including premotor cortex. Accordingly, impaired action verb knowledge in patients with amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD) is thought to be due to motor system degeneration. Upper motor neuron disease in ALS degrades the motor cortex and related pyramidal motor system, while disease in PD is centered in the basal ganglia and can spread to frontostriatal areas that are important to language functioning. These anatomical distinctions in disease may yield subtle differences in the action verb impairment between patient groups. Here we compare verbs where the body is the agent of the action to verbs where the body is the theme. To examine the role of motor functioning in body verb production, we split patient groups into patients with high motor impairment (HMI) and those with low motor impairment (LMI), using disease-specific measures of motor impairment. Regression analyses assessed how verb production in ALS and PD was related to motor system atrophy. We find a dissociation between agent- and theme-body verbs in ALS: ALS HMI were impaired for agent body verbs but not theme verbs, compared to ALS LMI. This dissociation was not present in PD patients, who instead show depressed production for all body verbs. Although patients with cognitive impairment were excluded from this study, cognitive performance significantly correlated with the production of theme verbs in ALS and cognitive/stative verbs in PD. Finally, regression analyses related the agent-theme dissociation in ALS to grey matter atrophy of premotor cortex. These findings support the view that motor dysfunction and disease in premotor cortex contributes to the agent body verb deficit in ALS, and begin to identify some distinct characteristics of impairment for verbs in ALS and PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cortico-hippocampal systems involved in memory and cognition: the PMAT framework.

PubMed

Ritchey, Maureen; Libby, Laura A; Ranganath, Charan

2015-01-01

In this chapter, we review evidence that the cortical pathways to the hippocampus appear to extend from two large-scale cortical systems: a posterior medial (PM) system that includes the parahippocampal cortex and retrosplenial cortex, and an anterior temporal (AT) system that includes the perirhinal cortex. This "PMAT" framework accounts for differences in the anatomical and functional connectivity of the medial temporal lobes, which may underpin differences in cognitive function between the systems. The PM and AT systems make distinct contributions to memory and to other cognitive domains, and convergent findings suggest that they are involved in processing information about contexts and items, respectively. In order to support the full complement of memory-guided behavior, the two systems must interact, and the hippocampal and ventromedial prefrontal cortex may serve as sites of integration between the two systems. We conclude that when considering the "connected hippocampus," inquiry should extend beyond the medial temporal lobes to include the large-scale cortical systems of which they are a part. © 2015 Elsevier B.V. All rights reserved.

The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease.

PubMed

Joubert, Sven; Brambati, Simona M; Ansado, Jennyfer; Barbeau, Emmanuel J; Felician, Olivier; Didic, Mira; Lacombe, Jacinthe; Goldstein, Rachel; Chayer, Céline; Kergoat, Marie-Jeanne

2010-03-01

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Effects of penetrating traumatic brain injury on event segmentation and memory.

PubMed

Zacks, Jeffrey M; Kurby, Christopher A; Landazabal, Claudia S; Krueger, Frank; Grafman, Jordan

2016-01-01

Penetrating traumatic brain injury (pTBI) is associated with deficits in cognitive tasks including comprehension and memory, and also with impairments in tasks of daily living. In naturalistic settings, one important component of cognitive task performance is event segmentation, the ability to parse the ongoing stream of behavior into meaningful units. Event segmentation ability is associated with memory performance and with action control, but is not well assessed by standard neuropsychological assessments or laboratory tasks. Here, we measured event segmentation and memory in a sample of 123 male military veterans aged 59-81 who had suffered a traumatic brain injury as young men, and 34 demographically similar controls. Participants watched movies of everyday activities and segmented them to identify fine-grained or coarse-grained events, and then completed tests of recognition memory for pictures from the movies and of memory for the temporal order of actions in the movies. Lesion location and volume were assessed with computed tomography (CT) imaging. Patients with traumatic brain injury were impaired on event segmentation. Those with larger lesions had larger impairments for fine segmentation and also impairments for both memory measures. Further, the degree of memory impairment was statistically mediated by the degree of event segmentation impairment. There was some evidence that lesions to the ventromedial prefrontal cortex (vmPFC) selectively impaired coarse segmentation; however, lesions outside of a priori regions of interest also were associated with impaired segmentation. One possibility is that the effect of vmPFC damage reflects the role of prefrontal event knowledge representations in ongoing comprehension. These results suggest that assessment of naturalistic event comprehension can be a valuable component of cognitive assessment in cases of traumatic brain injury, and that interventions aimed at event segmentation could be clinically helpful. Copyright © 2015 Elsevier Ltd. All rights reserved.

Representation of action in occipito-temporal cortex.

PubMed

Wiggett, Alison J; Downing, Paul E

2011-07-01

A fundamental question for social cognitive neuroscience is how and where in the brain the identities and actions of others are represented. Here we present a replication and extension of a study by Kable and Chatterjee [Kable, J. W., & Chatterjee, A. Specificity of action representations in the lateral occipito-temporal cortex. Journal of Cognitive Neuroscience, 18, 1498-1517, 2006] examining the role of occipito-temporal cortex in these processes. We presented full-cue movies of actors performing whole-body actions and used fMRI to test for action- and identity-specific adaptation effects. We examined a series of functionally defined regions, including the extrastriate and fusiform body areas, the fusiform face area, the parahippocampal place area, the lateral occipital complex, the right posterior superior temporal sulcus, and motion-selective area hMT+. These regions were analyzed with both standard univariate measures as well as multivoxel pattern analyses. Additionally, we performed whole-brain tests for significant adaptation effects. We found significant action-specific adaptation in many areas, but no evidence for identity-specific adaptation. We argue that this finding could be explained by differences in the familiarity of the stimuli presented: The actions shown were familiar but the actors performing the actions were unfamiliar. However, in contrast to previous findings, we found that the action adaptation effect could not be conclusively tied to specific functionally defined regions. Instead, our results suggest that the adaptation to previously seen actions across identities is a widespread effect, evident across lateral and ventral occipito-temporal cortex.

Effects of Head Impact Acceleration on Human Performance: Overview and Preliminary Battery Identification.

DTIC Science & Technology

1983-05-01

A. L. Personal communication. 1982. Benton, A. L., & Van Allen, M. W. Impairment in facial recognition in patients with cerebral disease. Cortex...patients. Journal of Consulting and Clinical Psycholology, 1977, 45, 684-688. (a) Levin, H. S., Grossman, R. G., Kelly, P. J. Impairment of facial ... recognition after closed head injuries of varying severity. Cortex, 1977, 13, 110-130. (b) Miller, E. Simple and choice reaction time following severe

Speech sound discrimination training improves auditory cortex responses in a rat model of autism

PubMed Central

Engineer, Crystal T.; Centanni, Tracy M.; Im, Kwok W.; Kilgard, Michael P.

2014-01-01

Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA) increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field (AAF) responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes. PMID:25140133

Cognitive and affective theory of mind share the same local patterns of activity in posterior temporal but not medial prefrontal cortex

PubMed Central

Hofstetter, Christoph; Vuilleumier, Patrik

2014-01-01

Understanding emotions in others engages specific brain regions in temporal and medial prefrontal cortices. These activations are often attributed to more general cognitive ‘mentalizing’ functions, associated with theory of mind and also necessary to represent people’s non-emotional mental states, such as beliefs or intentions. Here, we directly investigated whether understanding emotional feelings recruit similar or specific brain systems, relative to other non-emotional mental states. We used functional magnetic resonance imaging with multivoxel pattern analysis in 46 volunteers to compare activation patterns in theory-of-mind tasks for emotions, relative to beliefs or somatic states accompanied with pain. We found a striking dissociation between the temporoparietal cortex, that exhibited a remarkable voxel-by-voxel pattern overlap between emotions and beliefs (but not pain), and the dorsomedial prefrontal cortex, that exhibited distinct (and yet nearby) patterns of activity during the judgment of beliefs and emotions in others. Pain judgment was instead associated with activity in the supramarginal gyrus, middle cingulate cortex and middle insular cortex. Our data reveal for the first time a functional dissociation within brain networks sub-serving theory of mind for different mental contents, with a common recruitment for cognitive and affective states in temporal regions, and distinct recruitment in prefrontal areas. PMID:23770622

Parahippocampal Cortex Mediates the Relationship between Lutein and Crystallized Intelligence in Healthy, Older Adults

PubMed Central

Zamroziewicz, Marta K.; Paul, Erick J.; Zwilling, Chris E.; Johnson, Elizabeth J.; Kuchan, Matthew J.; Cohen, Neal J.; Barbey, Aron K.

2016-01-01

Introduction: Although, diet has a substantial influence on the aging brain, the relationship between dietary nutrients and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between a carotenoid important for brain health across the lifespan, lutein, and crystallized intelligence in cognitively intact older adults. We hypothesized that higher serum levels of lutein are associated with better performance on a task of crystallized intelligence, and that this relationship is mediated by gray matter structure of regions within the temporal cortex. This investigation aims to contribute to a growing line of evidence, which suggests that particular nutrients may slow or prevent aspects of cognitive decline by targeting specific features of brain aging. Methods: We examined 76 cognitively intact adults between the ages of 65 and 75 to investigate the relationship between serum lutein, tests of crystallized intelligence (measured by the Wechsler Abbreviated Scale of Intelligence), and gray matter volume of regions within the temporal cortex. A three-step mediation analysis was implemented using multivariate linear regressions to control for age, sex, education, income, depression status, and body mass index. Results: The mediation analysis revealed that gray matter thickness of one region within the temporal cortex, the right parahippocampal cortex (Brodmann's Area 34), partially mediates the relationship between serum lutein and crystallized intelligence. Conclusion: These results suggest that the parahippocampal cortex acts as a mediator of the relationship between serum lutein and crystallized intelligence in cognitively intact older adults. Prior findings substantiate the individual relationships reported within the mediation, specifically the links between (i) serum lutein and temporal cortex structure, (ii) serum lutein and crystallized intelligence, and (iii) parahippocampal cortex structure and crystallized intelligence. This report demonstrates a novel structural mediation between lutein status and crystallized intelligence, and therefore provides further evidence that specific nutrients may slow or prevent features of cognitive decline by hindering particular aspects of brain aging. Future work should examine the potential mechanisms underlying this mediation, including the antioxidant, anti-inflammatory, and membrane modulating properties of lutein. PMID:27999541

Flexible timing by temporal scaling of cortical responses

PubMed Central

Wang, Jing; Narain, Devika; Hosseini, Eghbal A.; Jazayeri, Mehrdad

2017-01-01

Musicians can perform at different tempos, speakers can control the cadence of their speech, and children can flexibly vary their temporal expectations of events. To understand the neural basis of such flexibility, we recorded from the medial frontal cortex of nonhuman primates trained to produce different time intervals with different effectors. Neural responses were heterogeneous, nonlinear and complex, and exhibited a remarkable form of temporal invariance: firing rate profiles were temporally scaled to match the produced intervals. Recording from downstream neurons in the caudate and thalamic neurons projecting to the medial frontal cortex indicated that this phenomenon originates within cortical networks. Recurrent neural network models trained to perform the task revealed that temporal scaling emerges from nonlinearities in the network and degree of scaling is controlled by the strength of external input. These findings demonstrate a simple and general mechanism for conferring temporal flexibility upon sensorimotor and cognitive functions. PMID:29203897

Selectivity of Local Field Potentials in Macaque Inferior Temporal Cortex

DTIC Science & Technology

2004-09-01

Selectivity of Local Field Potentials in Macaque Inferior Temporal Cortex Gabriel Kreiman , Chou Hung, Tomaso Poggio and James DiCarlo AI Memo 2004...IT. Note: Gabriel Kreiman and Chou Hung contributed equally to this work This report describes research done within the Center for Biological...separate the neuronal components of the MUA by using spike sorting algorithms (Quiroga et al., 2004; Yu and Kreiman , 1999). It will be interesting to

Functionally defined white matter reveals segregated pathways in human ventral temporal cortex associated with category-specific processing

PubMed Central

Gomez, Jesse; Pestilli, Franco; Witthoft, Nathan; Golarai, Golijeh; Liberman, Alina; Poltoratski, Sonia; Yoon, Jennifer; Grill-Spector, Kalanit

2014-01-01

Summary It is unknown if the white matter properties associated with specific visual networks selectively affect category-specific processing. In a novel protocol we combined measurements of white matter structure, functional selectivity, and behavior in the same subjects. We find two parallel white matter pathways along the ventral temporal lobe connecting to either face-selective or place-selective regions. Diffusion properties of portions of these tracts adjacent to face- and place-selective regions of ventral temporal cortex correlate with behavioral performance for face or place processing, respectively. Strikingly, adults with developmental prosopagnosia (face blindness) express an atypical structure-behavior relationship near face-selective cortex, suggesting that white matter atypicalities in this region may have behavioral consequences. These data suggest that examining the interplay between cortical function, anatomical connectivity, and visual behavior is integral to understanding functional networks and their role in producing visual abilities and deficits. PMID:25569351

Musical Creativity “Revealed” in Brain Structure: Interplay between Motor, Default Mode, and Limbic Networks

PubMed Central

Bashwiner, David M.; Wertz, Christopher J.; Flores, Ranee A.; Jung, Rex E.

2016-01-01

Creative behaviors are among the most complex that humans engage in, involving not only highly intricate, domain-specific knowledge and skill, but also domain-general processing styles and the affective drive to create. This study presents structural imaging data indicating that musically creative people (as indicated by self-report) have greater cortical surface area or volume in a) regions associated with domain-specific higher-cognitive motor activity and sound processing (dorsal premotor cortex, supplementary and pre-supplementary motor areas, and planum temporale), b) domain-general creative-ideation regions associated with the default mode network (dorsomedial prefrontal cortex, middle temporal gyrus, and temporal pole), and c) emotion-related regions (orbitofrontal cortex, temporal pole, and amygdala). These findings suggest that domain-specific musical expertise, default-mode cognitive processing style, and intensity of emotional experience might all coordinate to motivate and facilitate the drive to create music. PMID:26888383

Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

ERIC Educational Resources Information Center

Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

2015-01-01

Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer's disease.

PubMed

Zhang, Xiuming; Mormino, Elizabeth C; Sun, Nanbo; Sperling, Reisa A; Sabuncu, Mert R; Yeo, B T Thomas

2016-10-18

We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer's disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid-positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.

Componential Network for the Recognition of Tool-Associated Actions: Evidence from Voxel-based Lesion-Symptom Mapping in Acute Stroke Patients.

PubMed

Martin, Markus; Dressing, Andrea; Bormann, Tobias; Schmidt, Charlotte S M; Kümmerer, Dorothee; Beume, Lena; Saur, Dorothee; Mader, Irina; Rijntjes, Michel; Kaller, Christoph P; Weiller, Cornelius

2017-08-01

The study aimed to elucidate areas involved in recognizing tool-associated actions, and to characterize the relationship between recognition and active performance of tool use.We performed voxel-based lesion-symptom mapping in a prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male, age mean ± standard deviation, 65 ± 13 years; examination 4.4 ± 2 days post-stroke). In a video-based test, patients distinguished correct tool-related actions from actions with spatio-temporal (incorrect grip, kinematics, or tool orientation) or conceptual errors (incorrect tool-recipient matching, e.g., spreading jam on toast with a paintbrush). Moreover, spatio-temporal and conceptual errors were determined during actual tool use.Deficient spatio-temporal error discrimination followed lesions within a dorsal network in which the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were specifically relevant for assessing functional hand postures and kinematics, respectively. Conversely, impaired recognition of conceptual errors resulted from damage to ventral stream regions including anterior temporal lobe. Furthermore, LTC and IPL lesions impacted differently on action recognition and active tool use, respectively.In summary, recognition of tool-associated actions relies on a componential network. Our study particularly highlights the dissociable roles of LTC and IPL for the recognition of action kinematics and functional hand postures, respectively. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[FREQUENCY-TEMPORAL STRUCTURE OF HUMAN ELECTROENCEPHALOGRAM IN THE CONDITION OF ARTIFICIAL HYPOGRAVITY: DRY IMMERSION MODEL].

PubMed

Kuznetsova, G D; Gabova, A V; Lazarev, I E; Obukhov, Iu V; Obukhov, K Iu; Morozov, A A; Kulikov, M A; Shchatskova, A B; Vasil'eva, O N; Tomilovskaia, E S

2015-01-01

Frequency-temporal electroencephalogram (EEG) reactions to hypogravity were studied in 7 male subjects at the age of 20 to 27 years. The experiment was conducted using dry immersion (DI) as the best known method of simulating the space microgravity effects on the Earth. This hypogravity model reproduces hypokinesia, i.e. the weight-bearing and mechanic load removal, which is typical of microgravity. EEG was recorded by Neuroscan-2 (Compumedics) before the experiment (baseline data) and at the end of day 2 in DI. Comparative analysis of the EEG frequency-temporal structure was performed with the use of 2 techniques: Fourier transform and modified wavelet analysis. The Fourier transform elicited that after 2 days in DI the main shifts occurring to the EEG spectral composition are a decline in the alpha power and a slight though reliable growth of theta power. Similar frequency shifts were detected in the same records analyzed using the wavelet transform. According to wavelet analysis, during DI shifts in EEG frequency spectrum are accompanied by frequency desorganization of the EEG dominant rhythm and gross impairment of total stability of the electrical activity with time. Wavelet transform provides an opportunity to quantify changes in the frequency-temporal structure of the electrical activity of the brain. Quantitative evidence of frequency desorganization and temporal instability of EEG wavelet spectrograms may be the key to the understanding of mechanisms that drive functional disorders in the brain cortex in the conditions of hypogravity.

Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

PubMed

Nikolakaros, Georgios; Ilonen, Tuula; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G; Vataja, Risto

2016-11-15

Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease.

PubMed

Kashani, Alireza; Lepicard, Eve; Poirel, Odile; Videau, Catherine; David, Jean Philippe; Fallet-Bianco, Catherine; Simon, Axelle; Delacourte, André; Giros, Bruno; Epelbaum, Jacques; Betancur, Catalina; El Mestikawy, Salah

2008-11-01

Several lines of evidence suggest that the glutamatergic system is severely impaired in Alzheimer disease (AD). Here, we assessed the status of glutamatergic terminals in AD using the first available specific markers, the vesicular glutamate transporters VGLUT1 and VGLUT2. We quantified VGLUT1 and VGLUT2 in the prefrontal dorsolateral cortex (Brodmann area 9) of controls and AD patients using specific antiserums. A dramatic decrease in VGLUT1 and VGLUT2 was observed in AD using Western blot. Similar decreases were observed in an independent group of subjects using immunoautoradiography. The VGLUT1 reduction was highly correlated with the degree of cognitive impairment, assessed with the clinical dementia rating (CDR) score. A significant albeit weaker correlation was also observed with VGLUT2. These findings provide evidence indicating that glutamatergic systems are severely impaired in the A9 region of AD patients and that this impairment is strongly correlated with the progression of cognitive decline. Our results suggest that VGLUT1 expression in the prefrontal cortex could be used as a valuable neurochemical marker of dementia in AD.

Neuronal substrates of Corsi Block span: Lesion symptom mapping analyses in relation to attentional competition and spatial bias.

PubMed

Chechlacz, Magdalena; Rotshtein, Pia; Humphreys, Glyn W

2014-11-01

Spatial working memory problems are frequently reported following brain damage within both left and right hemispheres but with the severity often being grater in individuals with right hemisphere lesions. Clinically, deficits in spatial working memory have also been noted in patients with visuospatial disorders such as unilateral neglect. Here, we examined neural substrates of short-term memory for spatial locations based on the Corsi Block tapping task and the relationship with the visuospatial deficits of neglect and extinction in a group of chronic neuropsychological patients. Principal Component Analysis (PCA) was used to distinguish shared and dissociate functional components. The neural substrates of spatial short-term memory deficits and the components identified by PCA were examined using whole brain voxel-based morphometry and tract-wise lesion deficits analyses. We found that bilateral lesions within occipital cortex (middle occipital gyrus) and right posterior parietal cortex, along with disconnection of the right parieto-temporal segment of arcuate fasciculus, were associated with low spatial memory span. A single component revealed by PCA accounted for over half of the variance and was linked to damage to right posterior brain regions (temporo-parietal junction, the inferior parietal lobule and middle temporal gyrus extending into middle occipital gyrus). We also found link to disconnections within several association pathways including the superior longitudinal fasciculus, arcuate fasciculus, inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. These results indicate that different visuospatial deficits converge into a single component mapped within posterior parietal areas and fronto-parietal white matter pathways. Furthermore, the data presented here fit with the role of posterior parietal cortex/temporo-parietal junction in maintaining a map of salient locations in space, with Corsi Block performance being impaired when the spatial map is damaged. Copyright © 2014 Elsevier Ltd. All rights reserved.

Time Determines the Neural Circuit Underlying Associative Fear Learning

PubMed Central

Guimarãis, Marta; Gregório, Ana; Cruz, Andreia; Guyon, Nicolas; Moita, Marta A.

2011-01-01

Ultimately associative learning is a function of the temporal features and relationships between experienced stimuli. Nevertheless how time affects the neural circuit underlying this form of learning remains largely unknown. To address this issue, we used single-trial auditory trace fear conditioning and varied the length of the interval between tone and foot-shock. Through temporary inactivation of the amygdala, medial prefrontal-cortex (mPFC), and dorsal-hippocampus in rats, we tested the hypothesis that different temporal intervals between the tone and the shock influence the neuronal structures necessary for learning. With this study we provide the first experimental evidence showing that temporarily inactivating the amygdala before training impairs auditory fear learning when there is a temporal gap between the tone and the shock. Moreover, imposing a short interval (5 s) between the two stimuli also relies on the mPFC, while learning the association across a longer interval (40 s) becomes additionally dependent on a third structure, the dorsal-hippocampus. Thus, our results suggest that increasing the interval length between tone and shock leads to the involvement of an increasing number of brain areas in order for the association between the two stimuli to be acquired normally. These findings demonstrate that the temporal relationship between events is a key factor in determining the neuronal mechanisms underlying associative fear learning. PMID:22207842

Imaging the Spatio-Temporal Dynamics of Supragranular Activity in the Rat Somatosensory Cortex in Response to Stimulation of the Paws

PubMed Central

Morales-Botello, M. L.; Aguilar, J.; Foffani, G.

2012-01-01

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli. PMID:22829873

Diminished glucose transport and phosphorylation in Alzheimer`s disease determined by dynamic FDG-PET

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

Piert, M.; Koeppe, R.A.; Giordani, B.

1996-02-01

Using dynamic [{sup 18}F] fluorodeoxyglucose (FDG) and PET, kinetic rate constants that describe influx (K{sub 1}) and efflux (k{sub 2}) of FDG as well s phosphorylation (k{sub 3}) and dephosphorylation (k{sub 4}) were determined in patients with probable Alzheimer`s disease and similarly aged normal controls. The regional cerebral metabolic rate for glucose (CMR{sub glu}) was calculated from individually fitted rate constants in frontal, temporal, parietal and occipital cerebral cortex, caudate nucleus, putamen, thalamus and cerebellar cortex. Dynamic PET scans were obtained in normal controls (n = 10, mean age = 67) and Alzheimer`s disease patients (n = 8, mean agemore » = 67) for 60 min following injection of 10 mCi of FDG. The Alzheimer`s disease group was characterized by decreases of the CMR{sub glu} ranging from 13.3% in the frontal to 40.9% in the parietal cortex, which achieved significance in all regions except the thalamus. K{sub 1} was significantly reduced in the parietal (p < 0.01) and temporal cortices (p < 0.005), temporal and occipital cortex, and in the putamen and cerebellum (p < 0.05). The rate constants k{sub 2} and k{sub 4} were unchanged in the Alzheimer`s disease group. These data suggest that hypometabolism in Alzheimer`s disease is related to reduced glucose phosphorylation activity as well as diminished glucose transport, particularly in the most metabolically affected areas of the brain, the parietal and temporal cortex. 60 refs., 2 figs., 2 tabs.« less

Neural correlates of conversion disorder: overview and meta-analysis of neuroimaging studies on motor conversion disorder.

PubMed

Boeckle, Markus; Liegl, Gregor; Jank, Robert; Pieh, Christoph

2016-06-10

Conversion Disorders (CD) are prevalent functional disorders. Although the pathogenesis is still not completely understood, an interaction of genetic, neurobiological, and psychosocial factors is quite likely. The aim of this study is to provide a systematic overview on imaging studies on CDs and investigate neuronal areas involved in Motor Conversion Disorders (MCD). A systematic literature search was conducted on CD. Subsequently a meta-analysis of functional neuroimaging studies on MCD was implemented using an Activation Likelihood Estimation (ALE). We calculated differences between patients and healthy controls as well as between affected versus unaffected sides in addition to an overall analysis in order to identify neuronal areas related to MCD. Patients with MCD differ from healthy controls in the amygdala, superior temporal lobe, retrosplenial area, primary motor cortex, insula, red nucleus, thalamus, anterior as well as dorsolateral prefrontal and frontal cortex. When comparing affected versus unaffected sides, temporal cortex, dorsal anterior cingulate cortex, supramarginal gyrus, dorsal temporal lobe, anterior insula, primary somatosensory cortex, superior frontal gyrus and anterior prefrontal as well as frontal cortex show significant differences. Neuronal areas seem to be involved in the pathogenesis, maintenance or as a result of MCD. Areas that are important for motor-planning, motor-selection or autonomic response seem to be especially relevant. Our results support the emotional unawareness theory but also underline the need of more support by conduction imaging studies on both CD and MCD.

fMR-adaptation indicates selectivity to audiovisual content congruency in distributed clusters in human superior temporal cortex.

PubMed

van Atteveldt, Nienke M; Blau, Vera C; Blomert, Leo; Goebel, Rainer

2010-02-02

Efficient multisensory integration is of vital importance for adequate interaction with the environment. In addition to basic binding cues like temporal and spatial coherence, meaningful multisensory information is also bound together by content-based associations. Many functional Magnetic Resonance Imaging (fMRI) studies propose the (posterior) superior temporal cortex (STC) as the key structure for integrating meaningful multisensory information. However, a still unanswered question is how superior temporal cortex encodes content-based associations, especially in light of inconsistent results from studies comparing brain activation to semantically matching (congruent) versus nonmatching (incongruent) multisensory inputs. Here, we used fMR-adaptation (fMR-A) in order to circumvent potential problems with standard fMRI approaches, including spatial averaging and amplitude saturation confounds. We presented repetitions of audiovisual stimuli (letter-speech sound pairs) and manipulated the associative relation between the auditory and visual inputs (congruent/incongruent pairs). We predicted that if multisensory neuronal populations exist in STC and encode audiovisual content relatedness, adaptation should be affected by the manipulated audiovisual relation. The results revealed an occipital-temporal network that adapted independently of the audiovisual relation. Interestingly, several smaller clusters distributed over superior temporal cortex within that network, adapted stronger to congruent than to incongruent audiovisual repetitions, indicating sensitivity to content congruency. These results suggest that the revealed clusters contain multisensory neuronal populations that encode content relatedness by selectively responding to congruent audiovisual inputs, since unisensory neuronal populations are assumed to be insensitive to the audiovisual relation. These findings extend our previously revealed mechanism for the integration of letters and speech sounds and demonstrate that fMR-A is sensitive to multisensory congruency effects that may not be revealed in BOLD amplitude per se.

The 5% difference: early sensory processing predicts sarcasm perception in schizophrenia and schizo-affective disorder.

PubMed

Kantrowitz, J T; Hoptman, M J; Leitman, D I; Silipo, G; Javitt, D C

2014-01-01

Intact sarcasm perception is a crucial component of social cognition and mentalizing (the ability to understand the mental state of oneself and others). In sarcasm, tone of voice is used to negate the literal meaning of an utterance. In particular, changes in pitch are used to distinguish between sincere and sarcastic utterances. Schizophrenia patients show well-replicated deficits in auditory function and functional connectivity (FC) within and between auditory cortical regions. In this study we investigated the contributions of auditory deficits to sarcasm perception in schizophrenia. Auditory measures including pitch processing, auditory emotion recognition (AER) and sarcasm detection were obtained from 76 patients with schizophrenia/schizo-affective disorder and 72 controls. Resting-state FC (rsFC) was obtained from a subsample and was analyzed using seeds placed in both auditory cortex and meta-analysis-defined core-mentalizing regions relative to auditory performance. Patients showed large effect-size deficits across auditory measures. Sarcasm deficits correlated significantly with general functioning and impaired pitch processing both across groups and within the patient group alone. Patients also showed reduced sensitivity to alterations in mean pitch and variability. For patients, sarcasm discrimination correlated exclusively with the level of rsFC within primary auditory regions whereas for controls, correlations were observed exclusively within core-mentalizing regions (the right posterior superior temporal gyrus, anterior superior temporal sulcus and insula, and left posterior medial temporal gyrus). These findings confirm the contribution of auditory deficits to theory of mind (ToM) impairments in schizophrenia, and demonstrate that FC within auditory, but not core-mentalizing, regions is rate limiting with respect to sarcasm detection in schizophrenia.

Dissociation and Convergence of the Dorsal and Ventral Visual Streams in the Human Prefrontal Cortex

PubMed Central

Takahashi, Emi; Ohki, Kenichi; Kim, Dae-Shik

2012-01-01

Visual information is largely processed through two pathways in the primate brain: an object pathway from the primary visual cortex to the temporal cortex (ventral stream) and a spatial pathway to the parietal cortex (dorsal stream). Whether and to what extent dissociation exists in the human prefrontal cortex (PFC) has long been debated. We examined anatomical connections from functionally defined areas in the temporal and parietal cortices to the PFC, using noninvasive functional and diffusion-weighted magnetic resonance imaging. The right inferior frontal gyrus (IFG) received converging input from both streams, while the right superior frontal gyrus received input only from the dorsal stream. Interstream functional connectivity to the IFG was dynamically recruited only when both object and spatial information were processed. These results suggest that the human PFC receives dissociated and converging visual pathways, and that the right IFG region serves as an integrator of the two types of information. PMID:23063444

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

PubMed

Anderson, S W; Bechara, A; Damasio, H; Tranel, D; Damasio, A R

1999-11-01

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

Differing time dependencies of object recognition memory impairments produced by nicotinic and muscarinic cholinergic antagonism in perirhinal cortex

PubMed Central

Tinsley, Chris J.; Fontaine-Palmer, Nadine S.; Vincent, Maria; Endean, Emma P.E.; Aggleton, John P.; Brown, Malcolm W.; Warburton, E. Clea

2011-01-01

The roles of muscarinic and nicotinic cholinergic receptors in perirhinal cortex in object recognition memory were compared. Rats' discrimination of a novel object preference test (NOP) test was measured after either systemic or local infusion into the perirhinal cortex of the nicotinic receptor antagonist methyllycaconitine (MLA), which targets alpha-7 (α7) amongst other nicotinic receptors or the muscarinic receptor antagonists scopolamine, AFDX-384, and pirenzepine. Methyllycaconitine administered systemically or intraperirhinally before acquisition impaired recognition memory tested after a 24-h, but not a 20-min delay. In contrast, all three muscarinic antagonists produced a similar, unusual pattern of impairment with amnesia after a 20-min delay, but remembrance after a 24-h delay. Thus, the amnesic effects of nicotinic and muscarinic antagonism were doubly dissociated across the 20-min and 24-h delays. The same pattern of shorter-term but not longer-term memory impairment was found for scopolamine whether the object preference test was carried out in a square arena or a Y-maze and whether rats of the Dark Agouti or Lister-hooded strains were used. Coinfusion of MLA and either scopolamine or AFDX-384 produced an impairment profile matching that for MLA. Hence, the antagonists did not act additively when coadministered. These findings establish an important role in recognition memory for both nicotinic and muscarinic cholinergic receptors in perirhinal cortex, and provide a challenge to simple ideas about the role of cholinergic processes in recognition memory: The effects of muscarinic and nicotinic antagonism are neither independent nor additive. PMID:21693636

Differing time dependencies of object recognition memory impairments produced by nicotinic and muscarinic cholinergic antagonism in perirhinal cortex.

PubMed

Tinsley, Chris J; Fontaine-Palmer, Nadine S; Vincent, Maria; Endean, Emma P E; Aggleton, John P; Brown, Malcolm W; Warburton, E Clea

2011-01-01

The roles of muscarinic and nicotinic cholinergic receptors in perirhinal cortex in object recognition memory were compared. Rats' discrimination of a novel object preference test (NOP) test was measured after either systemic or local infusion into the perirhinal cortex of the nicotinic receptor antagonist methyllycaconitine (MLA), which targets alpha-7 (α7) amongst other nicotinic receptors or the muscarinic receptor antagonists scopolamine, AFDX-384, and pirenzepine. Methyllycaconitine administered systemically or intraperirhinally before acquisition impaired recognition memory tested after a 24-h, but not a 20-min delay. In contrast, all three muscarinic antagonists produced a similar, unusual pattern of impairment with amnesia after a 20-min delay, but remembrance after a 24-h delay. Thus, the amnesic effects of nicotinic and muscarinic antagonism were doubly dissociated across the 20-min and 24-h delays. The same pattern of shorter-term but not longer-term memory impairment was found for scopolamine whether the object preference test was carried out in a square arena or a Y-maze and whether rats of the Dark Agouti or Lister-hooded strains were used. Coinfusion of MLA and either scopolamine or AFDX-384 produced an impairment profile matching that for MLA. Hence, the antagonists did not act additively when coadministered. These findings establish an important role in recognition memory for both nicotinic and muscarinic cholinergic receptors in perirhinal cortex, and provide a challenge to simple ideas about the role of cholinergic processes in recognition memory: The effects of muscarinic and nicotinic antagonism are neither independent nor additive.

Baseline Brain Activity Changes in Patients With Single and Relapsing Optic Neuritis.

PubMed

Ren, Zhuoqiong; Liu, Yaou; Li, Kuncheng; Duan, Yunyun; Jing, Huang; Liang, Peipeng; Sun, Zheng; Zhang, Xiaojun; Mao, Bei

2018-01-01

Purpose : To investigate spontaneous brain activity amplitude alterations in single and relapsing optic neuritis (sON and rON, respectively) and their relationships with clinical variables. Methods : In total, 42 patients with sON, 35 patients with rON and 50 healthy volunteers were recruited. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) scans were acquired for all participants and compared to investigate the changes in the amplitude of low-frequency fluctuations (ALFFs) among the three groups. The relationships between the ALFFs in regions with significant differences in the groups and clinical variables, including the logarithm of minimal angle of resolution (LogMAR), Expanded Disability Status Scale (EDSS) score and disease duration, were further explored. Results : Compared with healthy volunteers, the sON and rON patients showed significantly decreased ALFFs in several regions of the occipital and temporal lobes (i.e., inferior occipital gyrus and superior temporal gyrus; corrected p < 0.01 using AlphaSim). The sON patients showed significantly increased ALFFs in the left caudate and certain regions in the frontal lobes (i.e., medial frontal gyrus), whereas the rON patients showed increased ALFFs in the bilateral inferior temporal gyrus and left medial frontal gyrus (corrected p < 0.01 using AlphaSim). Significantly decreased ALFFs were observed in the right inferior parietal lobule (IPL), left posterior cingulate and precuneus in the rON patients compared with those in the sON patients (corrected p < 0.01 using AlphaSim). Significant correlations were observed between the disease duration and ALFF in the left middle temporal gyrus, left inferior occipital gyrus, right lingual gyrus and right IPL ( p < 0.05). Conclusion : Functional impairment and adaptation occurred in both the sON and rON patients. Impairment mainly involved the occipital cortex, and functional adaptions predominantly occurred in the frontal lobe. Functional damage was more severe in the rON patients than in the sON patients and correlated with the disease duration.

Neuronal correlate of pictorial short-term memory in the primate temporal cortexYasushi Miyashita

NASA Astrophysics Data System (ADS)

Miyashita, Yasushi; Chang, Han Soo

1988-01-01

It has been proposed that visual-memory traces are located in the temporal lobes of the cerebral cortex, as electric stimulation of this area in humans results in recall of imagery1. Lesions in this area also affect recognition of an object after a delay in both humans2,3 and monkeys4-7 indicating a role in short-term memory of images8. Single-unit recordings from the temporal cortex have shown that some neurons continue to fire when one of two or four colours are to be remembered temporarily9. But neuronal responses selective to specific complex objects10-18 , including hands10,13 and faces13,16,17, cease soon after the offset of stimulus presentation10-18. These results led to the question of whether any of these neurons could serve the memory of complex objects. We report here a group of shape-selective neurons in an anterior ventral part of the temporal cortex of monkeys that exhibited sustained activity during the delay period of a visual short-term memory task. The activity was highly selective for the pictorial information to be memorized and was independent of the physical attributes such as size, orientation, colour or position of the object. These observations show that the delay activity represents the short-term memory of the categorized percept of a picture.

Visual cortex extrastriate body-selective area activation in congenitally blind people "seeing" by using sounds.

PubMed

Striem-Amit, Ella; Amedi, Amir

2014-03-17

Vision is by far the most prevalent sense for experiencing others' body shapes, postures, actions, and intentions, and its congenital absence may dramatically hamper body-shape representation in the brain. We investigated whether the absence of visual experience and limited exposure to others' body shapes could still lead to body-shape selectivity. We taught congenitally fully-blind adults to perceive full-body shapes conveyed through a sensory-substitution algorithm topographically translating images into soundscapes [1]. Despite the limited experience of the congenitally blind with external body shapes (via touch of close-by bodies and for ~10 hr via soundscapes), once the blind could retrieve body shapes via soundscapes, they robustly activated the visual cortex, specifically the extrastriate body area (EBA; [2]). Furthermore, body selectivity versus textures, objects, and faces in both the blind and sighted control groups was not found in the temporal (auditory) or parietal (somatosensory) cortex but only in the visual EBA. Finally, resting-state data showed that the blind EBA is functionally connected to the temporal cortex temporal-parietal junction/superior temporal sulcus Theory-of-Mind areas [3]. Thus, the EBA preference is present without visual experience and with little exposure to external body-shape information, supporting the view that the brain has a sensory-independent, task-selective supramodal organization rather than a sensory-specific organization. Copyright © 2014 Elsevier Ltd. All rights reserved.

Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease.

PubMed

Aziz, Anne-Laure; Giusiano, Bernard; Joubert, Sven; Duprat, Lauréline; Didic, Mira; Gueriot, Claude; Koric, Lejla; Boucraut, José; Felician, Olivier; Ranjeva, Jean-Philippe; Guedj, Eric; Ceccaldi, Mathieu

2017-06-01

Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

The assessment of colour perception, naming and knowledge: a new test device with a case study.

PubMed

Pagani, Rossella; Bosco, Giovanna; Dalla Valle, Elisabetta; Capitani, Erminio; Laiacona, Marcella

2012-08-01

Besides ocular diseases, also cerebral damage may cause colour vision deficits; cerebral lesions may be associated with a variety of clinical conditions that impair colour processing. This study presents procedures and normative data for a rapid, comprehensive seven-test battery aimed at assessing colour perception, colour naming and object colour knowledge. The norms, obtained from 96 healthy Italian participants, allow normality/pathology judgements on the basis of one-sided tolerance limits, after adjusting the score of each test for the demographic variables of the proband subjects. We also report, as an example, use of the battery in a stroke patient; this patient was chosen because her lesion affected the left temporal-occipital cortex, an area sometimes associated with a deficit of colour processing. The patient resulted normal on colour perception and colour name retrieval, but defective on object colour knowledge probed using the stimulus name. For the sound definition of the functional locus of cognitive impairment at the single case level, a multi-faceted set of tasks is necessary.

Wada testing reveals frontal lateralization for the memorization of words and faces.

PubMed

Kelley, W M; Ojemann, J G; Wetzel, R D; Derdeyn, C P; Moran, C J; Cross, D T; Dowling, J L; Miller, J W; Petersen, S E

2002-01-01

Neuroimaging studies have suggested that specific regions of the frontal and medial temporal cortex are engaged during memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage the left regions while nonverbal materials primarily engage the right regions. An open question, however, has been to what extent frontal regions contribute to successful memory formation. The present study investigates this question using a reversible lesion technique known as the Wada test. Patients memorized words and unfamiliar faces while portions of their left and right hemispheres were temporarily anesthetized with sodium amytal. Subsequent memory tests revealed that faces were remembered better than words following left-hemisphere anesthesia, whereas words were remembered better than faces following right-hemisphere anesthesia. Importantly, inspection of the circulation affected by the amytal further suggests that these memory impairments did not result from direct anesthetization of the medial temporal regions. Taken in the context of the imaging findings, these results suggest that frontal regions may also contribute to memory formation in normal performance.

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice.

PubMed

Arime, Yosefu; Akiyama, Kazufumi

2017-01-01

Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice

PubMed Central

Akiyama, Kazufumi

2017-01-01

Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2–3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2–3 of the prelimbic cortex of the PFC. PMID:29253020

How sensory-motor systems impact the neural organization for language: direct contrasts between spoken and signed language

PubMed Central

Emmorey, Karen; McCullough, Stephen; Mehta, Sonya; Grabowski, Thomas J.

2014-01-01

To investigate the impact of sensory-motor systems on the neural organization for language, we conducted an H215O-PET study of sign and spoken word production (picture-naming) and an fMRI study of sign and audio-visual spoken language comprehension (detection of a semantically anomalous sentence) with hearing bilinguals who are native users of American Sign Language (ASL) and English. Directly contrasting speech and sign production revealed greater activation in bilateral parietal cortex for signing, while speaking resulted in greater activation in bilateral superior temporal cortex (STC) and right frontal cortex, likely reflecting auditory feedback control. Surprisingly, the language production contrast revealed a relative increase in activation in bilateral occipital cortex for speaking. We speculate that greater activation in visual cortex for speaking may actually reflect cortical attenuation when signing, which functions to distinguish self-produced from externally generated visual input. Directly contrasting speech and sign comprehension revealed greater activation in bilateral STC for speech and greater activation in bilateral occipital-temporal cortex for sign. Sign comprehension, like sign production, engaged bilateral parietal cortex to a greater extent than spoken language. We hypothesize that posterior parietal activation in part reflects processing related to spatial classifier constructions in ASL and that anterior parietal activation may reflect covert imitation that functions as a predictive model during sign comprehension. The conjunction analysis for comprehension revealed that both speech and sign bilaterally engaged the inferior frontal gyrus (with more extensive activation on the left) and the superior temporal sulcus, suggesting an invariant bilateral perisylvian language system. We conclude that surface level differences between sign and spoken languages should not be dismissed and are critical for understanding the neurobiology of language. PMID:24904497

A meta-analysis of neuroimaging studies on divergent thinking using activation likelihood estimation.

PubMed

Wu, Xin; Yang, Wenjing; Tong, Dandan; Sun, Jiangzhou; Chen, Qunlin; Wei, Dongtao; Zhang, Qinglin; Zhang, Meng; Qiu, Jiang

2015-07-01

In this study, an activation likelihood estimation (ALE) meta-analysis was used to conduct a quantitative investigation of neuroimaging studies on divergent thinking. Based on the ALE results, the functional magnetic resonance imaging (fMRI) studies showed that distributed brain regions were more active under divergent thinking tasks (DTTs) than those under control tasks, but a large portion of the brain regions were deactivated. The ALE results indicated that the brain networks of the creative idea generation in DTTs may be composed of the lateral prefrontal cortex, posterior parietal cortex [such as the inferior parietal lobule (BA 40) and precuneus (BA 7)], anterior cingulate cortex (ACC) (BA 32), and several regions in the temporal cortex [such as the left middle temporal gyrus (BA 39), and left fusiform gyrus (BA 37)]. The left dorsolateral prefrontal cortex (BA 46) was related to selecting the loosely and remotely associated concepts and organizing them into creative ideas, whereas the ACC (BA 32) was related to observing and forming distant semantic associations in performing DTTs. The posterior parietal cortex may be involved in the semantic information related to the retrieval and buffering of the formed creative ideas, and several regions in the temporal cortex may be related to the stored long-term memory. In addition, the ALE results of the structural studies showed that divergent thinking was related to the dopaminergic system (e.g., left caudate and claustrum). Based on the ALE results, both fMRI and structural MRI studies could uncover the neural basis of divergent thinking from different aspects (e.g., specific cognitive processing and stable individual difference of cognitive capability). © 2015 Wiley Periodicals, Inc.

Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

PubMed

Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

2014-01-01

Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

Perfusion network shift during seizures in medial temporal lobe epilepsy.

PubMed

Sequeira, Karen M; Tabesh, Ali; Sainju, Rup K; DeSantis, Stacia M; Naselaris, Thomas; Joseph, Jane E; Ahlman, Mark A; Spicer, Kenneth M; Glazier, Steve S; Edwards, Jonathan C; Bonilha, Leonardo

2013-01-01

Medial temporal lobe epilepsy (MTLE) is associated with limbic atrophy involving the hippocampus, peri-hippocampal and extra-temporal structures. While MTLE is related to static structural limbic compromise, it is unknown whether the limbic system undergoes dynamic regional perfusion network alterations during seizures. In this study, we aimed to investigate state specific (i.e. ictal versus interictal) perfusional limbic networks in patients with MTLE. We studied clinical information and single photon emission computed tomography (SPECT) images obtained with intravenous infusion of the radioactive tracer Technetium- Tc 99 m Hexamethylpropyleneamine Oxime (Tc-99 m HMPAO) during ictal and interictal state confirmed by video-electroencephalography (VEEG) in 20 patients with unilateral MTLE (12 left and 8 right MTLE). Pair-wise voxel-based analyses were used to define global changes in tracer between states. Regional tracer uptake was calculated and state specific adjacency matrices were constructed based on regional correlation of uptake across subjects. Graph theoretical measures were applied to investigate global and regional state specific network reconfigurations. A significant increase in tracer uptake was observed during the ictal state in the medial temporal region, cerebellum, thalamus, insula and putamen. From network analyses, we observed a relative decreased correlation between the epileptogenic temporal region and remaining cortex during the interictal state, followed by a surge of cross-correlated perfusion in epileptogenic temporal-limbic structures during a seizure, corresponding to local network integration. These results suggest that MTLE is associated with a state specific perfusion and possibly functional organization consisting of a surge of limbic cross-correlated tracer uptake during a seizure, with a relative disconnection of the epileptogenic temporal lobe in the interictal period. This pattern of state specific shift in metabolic networks in MTLE may improve the understanding of epileptogenesis and neuropsychological impairments associated with MTLE.

Prefrontal contributions to domain-general executive control processes during temporal context retrieval.

PubMed

Rajah, M Natasha; Ames, Blaine; D'Esposito, Mark

2008-03-07

Neuroimaging studies have reported increased prefrontal cortex (PFC) activity during temporal context retrieval versus recognition memory. However, it remains unclear if these activations reflect PFC contributions to domain-general executive control processes or domain-specific retrieval processes. To gain a better understanding of the functional roles of these various PFC regions during temporal context retrieval we propose it is necessary to examine PFC activity across tasks from different domains, in which parallel manipulations are included targeting specific cognitive processes. In the current fMRI study, we examined domain-general and domain-specific PFC contributions to temporal context retrieval by increasing stimulus (but maintaining response number) and increasing response number (but maintaining stimulus number) across temporal context memory and ordering control tasks, for faces. The control task required subjects to order faces from youngest to oldest. Our behavioral results indicate that the combination of increased stimulus and response numbers significantly increased task difficulty for temporal context retrieval and ordering tasks. Across domains, increasing stimulus number, while maintaining response numbers, caused greater right lateral premotor cortex (BA 6/8) activity; whereas increasing response number, while maintaining stimulus number, caused greater domain-general left DLPFC (BA 9) and VLPFC (BA 44/45) activity. In addition, we found domain-specific right DLPFC (BA 9) activity only during retrieval events. These results highlight the functional heterogeneity of frontal cortex, and suggest its involvement in temporal context retrieval is related to its role in various cognitive control processes.

Temporal information entropy of the Blood-Oxygenation Level-Dependent signals increases in the activated human primary visual cortex

NASA Astrophysics Data System (ADS)

DiNuzzo, Mauro; Mascali, Daniele; Moraschi, Marta; Bussu, Giorgia; Maraviglia, Bruno; Mangia, Silvia; Giove, Federico

2017-02-01

Time-domain analysis of blood-oxygenation level-dependent (BOLD) signals allows the identification of clusters of voxels responding to photic stimulation in primary visual cortex (V1). However, the characterization of information encoding into temporal properties of the BOLD signals of an activated cluster is poorly investigated. Here, we used Shannon entropy to determine spatial and temporal information encoding in the BOLD signal within the most strongly activated area of the human visual cortex during a hemifield photic stimulation. We determined the distribution profile of BOLD signals during epochs at rest and under stimulation within small (19-121 voxels) clusters designed to include only voxels driven by the stimulus as highly and uniformly as possible. We found consistent and significant increases (2-4% on average) in temporal information entropy during activation in contralateral but not ipsilateral V1, which was mirrored by an expected loss of spatial information entropy. These opposite changes coexisted with increases in both spatial and temporal mutual information (i.e. dependence) in contralateral V1. Thus, we showed that the first cortical stage of visual processing is characterized by a specific spatiotemporal rearrangement of intracluster BOLD responses. Our results indicate that while in the space domain BOLD maps may be incapable of capturing the functional specialization of small neuronal populations due to relatively low spatial resolution, some information encoding may still be revealed in the temporal domain by an increase of temporal information entropy.

Impaired "affective theory of mind" is associated with right ventromedial prefrontal damage.

PubMed

Shamay-Tsoory, S G; Tomer, R; Berger, B D; Goldsher, D; Aharon-Peretz, J

2005-03-01

To examine the hypothesis that patients with ventromedial (VM) frontal lesions are impaired in the affective rather than cognitive facets of theory of mind (ToM). Prefrontal brain damage may result in impaired social behavior, especially when the damage involves the orbitofrontal/VM prefrontal cortex (PFC). It has been previously suggested that deficits in ToM may account for such aberrant behavior. However, inconsistent results have been reported, and different regions within the frontal cortex have been associated with ToM impairment. The performance of 26 patients with localized lesions in the PFC was compared with responses of 13 patients with posterior lesions and 13 normal control subjects. Three ToM tasks differing in the level of emotional processing involved were used: second-order false belief task, understanding ironic utterances, and identifying social faux pas. The results indicated that patients with VM (but not dorsolateral) prefrontal lesions were significantly impaired in irony and faux pas but not in second-order false belief as compared with patients with posterior lesions and normal control subjects. Lesions in the right VM area were associated with the most severe ToM deficit. These results are discussed in terms of the cognitive and affective facets of "mind-reading" processes mediated by the VM cortex.

Interaction between the medial prefrontal cortex and hippocampal CA1 area is essential for episodic-like memory in rats.

PubMed

Chao, Owen Y; Nikolaus, Susanne; Lira Brandão, Marcus; Huston, Joseph P; de Souza Silva, Maria A

2017-05-01

The interplay between medial prefrontal cortex (mPFC) and hippocampus, particularly the hippocampal CA3 area, is critical for episodic memory. To what extent the mPFC also interacts with the hippocampus CA1 subregion still requires elucidation. To investigate this issue, male rats received unilateral N-methyl- D -aspartate lesions of the mPFC together with unilateral lesions of the hippocampal CA1 area, either in the same (control) or in the opposite hemispheres (disconnection). They underwent an episodic-like memory test, combining what-where-when information, and separate tests for novel object preference (what), object place preference (where) and temporal order memory (when). Compared to controls, the disconnected mPFC-CA1 rats exhibited disrupted episodic-like memory with an impaired integration of the what-where-when elements. Both groups showed intact memories for what and when, while only the control group showed intact memory for where. These findings suggest that the functional interaction of the mPFC-CA1 circuit is crucial for the processing of episodic memory and, in particular, for the integration of the spatial memory component. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural and functional changes of the cingulate gyrus following traumatic brain injury: relation to attention and executive skills.

PubMed

Merkley, Tricia L; Larson, Michael J; Bigler, Erin D; Good, Daniel A; Perlstein, William M

2013-09-01

Impairments of attention and executive functions are common sequelae of traumatic brain injury (TBI). The anterior cingulate is implicated in conflict-related task performance, such as the Stroop, and is susceptible to TBI-related injury due to its frontal location and proximity to the rough surface of the falx cerebri. We investigated the relationship between cingulate cortex volume and performance on tasks of selective attention and cognitive flexibility (single-trial Stroop and Auditory Consonant Trigrams [ACT]). Participants consisted of 12 adults with severe TBI and 18 controls. T1-weighted volumetric MRI data were analyzed using automated cortical reconstruction, segmentation, parcellation, and volume measurement. Cortical volume reductions were prominent bilaterally in frontal, temporal, and inferior parietal regions.Specific regional reduction of the cingulate cortex was observed only for cortical volume of right caudal anterior cingulate(cACC). The TBI group performed significantly worse than control participants on the Stroop and ACT tasks. Findings suggest that atrophy of the right cACC may contribute to reduced performance on executive function tasks, such as the Stroop and ACT, although this is likely but one node of an extensive brain network involved in these cognitive processes.

Theory of mind network activity is altered in subjects with familial liability for schizophrenia

PubMed Central

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Romanczuk-Seiferth, Nina; Schmierer, Phöbe; Romund, Lydia; Garbusow, Maria; Wackerhagen, Carolin; Ripke, Stephan; Grimm, Oliver; Haller, Leila; Witt, Stephanie H.; Degenhardt, Franziska; Tost, Heike; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2016-01-01

As evidenced by a multitude of studies, abnormalities in Theory of Mind (ToM) and its neural processing might constitute an intermediate phenotype of schizophrenia. If so, neural alterations during ToM should be observable in unaffected relatives of patients as well, since they share a considerable amount of genetic risk. While behaviorally, impaired ToM function is confirmed meta-analytically in relatives, evidence on aberrant function of the neural ToM network is sparse and inconclusive. The present study therefore aimed to further explore the neural correlates of ToM in relatives of schizophrenia. About 297 controls and 63 unaffected first-degree relatives of patients with schizophrenia performed a ToM task during functional magnetic resonance imaging. Consistent with the literature relatives exhibited decreased activity of the medial prefrontal cortex. Additionally, increased recruitment of the right middle temporal gyrus and posterior cingulate cortex was found, which was related to subclinical paranoid symptoms in relatives. These results further support decreased medial prefrontal activation during ToM as an intermediate phenotype of genetic risk for schizophrenia. Enhanced recruitment of posterior ToM areas in relatives might indicate inefficiency mechanisms in the presence of genetic risk. PMID:26341902

Injury to the Premature Cerebellum: Outcome is Related to Remote Cortical Development

PubMed Central

Limperopoulos, Catherine; Chilingaryan, Gevorg; Sullivan, Nancy; Guizard, Nicolas; Robertson, Richard L.; du Plessis, Adré J.

2014-01-01

Cerebellar injury is an important complication of preterm birth with far-reaching neuropsychiatric sequelae. We have previously shown a significant association between isolated injury to the premature cerebellum and subsequent impairment of regional volumetric growth in the contralateral cerebrum. In the current study, we examine the relationship between these remote regional impairments of cerebral volumetric growth and domain-specific functional deficits in these children. In 40 ex-preterm infants with isolated cerebellar injury, we performed neurodevelopmental evaluations and quantitative magnetic resonance imaging (MRI) studies at a mean age of 34 months. We measured cortical gray matter volumes in 8 parcellated regions of each cerebral hemisphere, as well as right and left cerebellar volumes. We show highly significant associations between early signs of autism and dorsolateral prefrontal cortex volume (P < 0.001); gross motor scores and sensorimotor cortical volumes (P < 0.001); and cognitive and expressive language scores and premotor and mid-temporal cortical volumes (P < 0.001). By multivariate analyses, each unit increase in the corresponding regional cerebral volume was associated with lower odds of abnormal outcome score, adjusted for age at MRI and contralateral cerebellar volume. This is the first report linking secondary impairment of remote cerebral cortical growth and functional disabilities in survivors of prematurity-related cerebellar brain injury. PMID:23146968

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.

A role for Kalirin-7 in corticostriatal synaptic dysfunction in Huntington's disease

PubMed Central

Puigdellívol, Mar; Cherubini, Marta; Brito, Verónica; Giralt, Albert; Suelves, Núria; Ballesteros, Jesús; Zamora-Moratalla, Alfonsa; Martín, Eduardo D.; Eipper, Betty A.; Alberch, Jordi; Ginés, Silvia

2015-01-01

Cognitive dysfunction is an early clinical hallmark of Huntington's disease (HD) preceding the appearance of motor symptoms by several years. Neuronal dysfunction and altered corticostriatal connectivity have been postulated to be fundamental to explain these early disturbances. However, no treatments to attenuate cognitive changes have been successful: the reason may rely on the idea that the temporal sequence of pathological changes is as critical as the changes per se when new therapies are in development. To this aim, it becomes critical to use HD mouse models in which cognitive impairments appear prior to motor symptoms. In this study, we demonstrate procedural memory and motor learning deficits in two different HD mice and at ages preceding motor disturbances. These impairments are associated with altered corticostriatal long-term potentiation (LTP) and specific reduction of dendritic spine density and postsynaptic density (PSD)-95 and spinophilin-positive clusters in the cortex of HD mice. As a potential mechanism, we described an early decrease of Kalirin-7 (Kal7), a guanine-nucleotide exchange factor for Rho-like small GTPases critical to maintain excitatory synapse, in the cortex of HD mice. Supporting a role for Kal7 in HD synaptic deficits, exogenous expression of Kal7 restores the reduction of excitatory synapses in HD cortical cultures. Altogether, our results suggest that cortical dysfunction precedes striatal disturbances in HD and underlie early corticostriatal LTP and cognitive defects. Moreover, we identified diminished Kal7 as a key contributor to HD cortical alterations, placing Kal7 as a molecular target for future therapies aimed to restore corticostriatal function in HD. PMID:26464483

Abnormal functional connectivity density in children with anisometropic amblyopia at resting-state.

PubMed

Wang, Tianyue; Li, Qian; Guo, Mingxia; Peng, Yanmin; Li, Qingji; Qin, Wen; Yu, Chunshui

2014-05-14

Amblyopia is a developmental disorder resulting from anomalous binocular visual input in early life. Task-based neuroimaging studies have widely investigated cortical functional impairments in amblyopia, but changes in spontaneous neuronal functional activities in amblyopia remain largely unknown. In the present study, functional connectivity density (FCD) mapping, an ultrafast data-driven method based on fMRI, was applied for the first time to investigate changes in cortical functional connectivities in amblyopia during the resting-state. We quantified and compared both short- and long-range FCD in both the brains of children with anisometropic amblyopia (AAC) and normal sighted children (NSC). In contrast to the NSC, the AAC showed significantly decreased short-range FCD in the inferior temporal/fusiform gyri, parieto-occipital and rostrolateral prefrontal cortices, as well as decreased long-range FCD in the premotor cortex, dorsal inferior parietal lobule, frontal-insular and dorsal prefrontal cortices. Furthermore, most regions with reduced long-range FCD in the AAC showed decreased functional connectivity with occipital and posterior parietal cortices in the AAC. The results suggest that chronically poor visual input in amblyopia not only impairs the brain's short-range functional connections in visual pathways and in the frontal cortex, which is important for cognitive control, but also affects long-range functional connections among the visual areas, posterior parietal and frontal cortices that subserve visuomotor and visual-guided actions, visuospatial attention modulation and the integration of salient information. This study provides evidence for abnormal spontaneous brain activities in amblyopia. Copyright © 2014 Elsevier B.V. All rights reserved.

Tau PET in Alzheimer disease and mild cognitive impairment.

PubMed

Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song; Lee, Jae Hoon; Kim, You Jin; Lee, Hye Mi; Lyoo, Chul Hyoung; Ryu, Young Hoon; Lee, Myung Sik

2016-07-26

To investigate the topographical distribution of tau pathology and its effect on functional and structural changes in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) by using (18)F-AV-1451 PET. We included 20 patients with AD, 15 patients with MCI, and 20 healthy controls, and performed neuropsychological function tests, MRI, as well as (18)F-florbetaben (for amyloid) and (18)F-AV-1451 (for tau) PET scans. By using the regional volume-of-interest masks extracted from MRIs, regional binding values of standardized uptake value ratios and volumes were measured. We compared regional binding values among 3 diagnostic groups and identified correlations among the regional binding values, performance in each cognitive function test, and regional atrophy. (18)F-AV-1451 binding was increased only in the entorhinal cortex in patients with MCI, while patients with AD exhibited greater binding in most cortical regions. In the 35 patients with MCI and AD, (18)F-AV-1451 binding in most of the neocortex increased with a worsening of global cognitive function. The visual and verbal memory functions were associated with the extent of (18)F-AV-1451 binding, especially in the medial temporal regions. The (18)F-AV-1451 binding also correlated with the severity of regional atrophy of the cerebral cortex. Tau PET imaging with (18)F-AV-1451 could serve as an in vivo biomarker for the evaluation of AD-related tau pathology and monitoring disease progression. The accumulation of pathologic tau is more closely related to functional and structural deterioration in the AD spectrum than β-amyloid. © 2016 American Academy of Neurology.

Abnormal regional cerebral blood flow in childhood autism.

PubMed

Ohnishi, T; Matsuda, H; Hashimoto, T; Kunihiro, T; Nishikawa, M; Uema, T; Sasaki, M

2000-09-01

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Ventromedial prefrontal cortex pyramidal cells have a temporal dynamic role in recall and extinction of cocaine-associated memory.

PubMed

Van den Oever, Michel C; Rotaru, Diana C; Heinsbroek, Jasper A; Gouwenberg, Yvonne; Deisseroth, Karl; Stuber, Garret D; Mansvelder, Huibert D; Smit, August B

2013-11-13

In addicts, associative memories related to the rewarding effects of drugs of abuse can evoke powerful craving and drug seeking urges, but effective treatment to suppress these memories is not available. Detailed insight into the neural circuitry that mediates expression of drug-associated memory is therefore of crucial importance. Substantial evidence from rodent models of addictive behavior points to the involvement of the ventromedial prefrontal cortex (vmPFC) in conditioned drug seeking, but specific knowledge of the temporal role of vmPFC pyramidal cells is lacking. To this end, we used an optogenetics approach to probe the involvement of vmPFC pyramidal cells in expression of a recent and remote conditioned cocaine memory. In mice, we expressed Channelrhodopsin-2 (ChR2) or Halorhodopsin (eNpHR3.0) in pyramidal cells of the vmPFC and studied the effect of activation or inhibition of these cells during expression of a cocaine-contextual memory on days 1-2 (recent) and ∼3 weeks (remote) after conditioning. Whereas optical activation of pyramidal cells facilitated extinction of remote memory, without affecting recent memory, inhibition of pyramidal cells acutely impaired recall of recent cocaine memory, without affecting recall of remote memory. In addition, we found that silencing pyramidal cells blocked extinction learning at the remote memory time-point. We provide causal evidence of a critical time-dependent switch in the contribution of vmPFC pyramidal cells to recall and extinction of cocaine-associated memory, indicating that the circuitry that controls expression of cocaine memories reorganizes over time.

Atypical spatiotemporal signatures of working memory brain processes in autism.

PubMed

Urbain, C M; Pang, E W; Taylor, M J

2015-08-11

Working memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM-related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed.

Person-Based Versus Generalized Impulsivity Disinhibition in Frontotemporal Dementia and Alzheimer Disease.

PubMed

Paholpak, Pongsatorn; Carr, Andrew R; Barsuglia, Joseph P; Barrows, Robin J; Jimenez, Elvira; Lee, Grace J; Mendez, Mario F

2016-09-19

While much disinhibition in dementia results from generalized impulsivity, in behavioral variant frontotemporal dementia (bvFTD) disinhibition may also result from impaired social cognition. To deconstruct disinhibition and its neural correlates in bvFTD vs. early-onset Alzheimer's disease (eAD). Caregivers of 16 bvFTD and 21 matched-eAD patients completed the Frontal Systems Behavior Scale disinhibition items. The disinhibition items were further categorized into (1) "person-based" subscale which predominantly associated with violating social propriety and personal boundary and (2) "generalized-impulsivity" subscale which included nonspecific impulsive acts. Subscale scores were correlated with grey matter volumes from tensor-based morphometry on magnetic resonance images. In comparison to the eAD patients, the bvFTD patients developed greater person-based disinhibition (P < 0.001) but comparable generalized impulsivity. Severity of person-based disinhibition significantly correlated with the left anterior superior temporal sulcus (STS), and generalized-impulsivity correlated with the right orbitofrontal cortex (OFC) and the left anterior temporal lobe (aTL). Person-based disinhibition was predominant in bvFTD and correlated with the left STS. In both dementia, violations of social propriety and personal boundaries involved fronto-parieto-temporal network of Theory of Mind, whereas nonspecific disinhibition involved the OFC and aTL. © The Author(s) 2016.

Long-term retrograde amnesia...the crucial role of the hippocampus.

PubMed

Cipolotti, L; Shallice, T; Chan, D; Fox, N; Scahill, R; Harrison, G; Stevens, J; Rudge, P

2001-01-01

For patients with hippocampal pathology, disagreement exists in the literature over whether retrograde amnesia is temporally limited or very extensive depending on whether the anatomical damage is restricted to this structure or also involves additional temporal cortex. We report a comprehensive assessment of retrograde and anterograde memory functions of a severely global amnesic patient (VC). We found that he presented with a remarkably extensive and basically ungraded retrograde amnesia. This impairment profoundly affected four decades preceding the onset of his amnesia and encompassed both non personal and personal facts and events. VC also presented with a severe anterograde amnesia and a deficit in the acquisition of new semantic knowledge in the post-morbid period. Detailed MRI volumetric measurements revealed gross abnormalities in both hippocampi which were markedly shrunken. Of relevance to the debate on retrograde amnesia were the observations that the volumes of both entorhinal cortices and the remainder of both temporal lobes were normal. These data suggest that the hippocampus is critical not only for the efficient encoding and hence normal recall of new information but also for the recall of episodic information acquired before the onset of amnesia. Our results are compatible with the view that retrograde amnesia is both extensive and ungraded when the damage is limited to the hippocampus.

Medial Temporal Lobe Contributions to Cued Retrieval of Items and Contexts

PubMed Central

Hannula, Deborah E.; Libby, Laura A.; Yonelinas, Andrew P.; Ranganath, Charan

2013-01-01

Several models have proposed that different regions of the medial temporal lobes contribute to different aspects of episodic memory. For instance, according to one view, the perirhinal cortex represents specific items, parahippocampal cortex represents information regarding the context in which these items were encountered, and the hippocampus represents item-context bindings. Here, we used event-related functional magnetic resonance imaging (fMRI) to test a specific prediction of this model – namely, that successful retrieval of items from context cues will elicit perirhinal recruitment and that successful retrieval of contexts from item cues will elicit parahippocampal cortex recruitment. Retrieval of the bound representation in either case was expected to elicit hippocampal engagement. To test these predictions, we had participants study several item-context pairs (i.e., pictures of objects and scenes, respectively), and then had them attempt to recall items from associated context cues and contexts from associated item cues during a scanned retrieval session. Results based on both univariate and multivariate analyses confirmed a role for hippocampus in content-general relational memory retrieval, and a role for parahippocampal cortex in successful retrieval of contexts from item cues. However, we also found that activity differences in perirhinal cortex were correlated with successful cued recall for both items and contexts. These findings provide partial support for the above predictions and are discussed with respect to several models of medial temporal lobe function. PMID:23466350

Frequency-Selective Attention in Auditory Scenes Recruits Frequency Representations Throughout Human Superior Temporal Cortex.

PubMed

Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

2017-05-01

A sound of interest may be tracked amid other salient sounds by focusing attention on its characteristic features including its frequency. Functional magnetic resonance imaging findings have indicated that frequency representations in human primary auditory cortex (AC) contribute to this feat. However, attentional modulations were examined at relatively low spatial and spectral resolutions, and frequency-selective contributions outside the primary AC could not be established. To address these issues, we compared blood oxygenation level-dependent (BOLD) responses in the superior temporal cortex of human listeners while they identified single frequencies versus listened selectively for various frequencies within a multifrequency scene. Using best-frequency mapping, we observed that the detailed spatial layout of attention-induced BOLD response enhancements in primary AC follows the tonotopy of stimulus-driven frequency representations-analogous to the "spotlight" of attention enhancing visuospatial representations in retinotopic visual cortex. Moreover, using an algorithm trained to discriminate stimulus-driven frequency representations, we could successfully decode the focus of frequency-selective attention from listeners' BOLD response patterns in nonprimary AC. Our results indicate that the human brain facilitates selective listening to a frequency of interest in a scene by reinforcing the fine-grained activity pattern throughout the entire superior temporal cortex that would be evoked if that frequency was present alone. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.