Intracranial cortical localization of the human K-complex

ObjectiveThe K-complex was first identified in human sleep EEG more than 70 years ago, but the localization of its intracranial generators is an unresolved issue. In this study, K-complexes recorded using simultaneous scalp and intracranial EEG were analyzed to discover the intracranial distribution of the human K-complex.MethodsStereoelectroencephalographic recordings were performed in six patients with medically-refractory epilepsy. Full 10–20 scalp montages were used and intracranial macroelectrodes sampled medial, lateral and basal frontal and temporal cortices, medial and lateral parietal and occipital cortices, as well as the hippocampus and thalamus. Spontaneous K-complexes were visually identified in stage II sleep and averaged off-line.ResultsThe intracranial K-complex field was maximal over the anterior and superior aspects of the medial and lateral frontal lobe cortices, consistent with the frontal midline scalp EEG maximum. The frontal maximum surface-negative field was volume conducted as an inverted, positive field posteriorly and inferiorly, the polarity reversing laterally above the inferior temporal region and medially above the cingulate cortex.ConclusionsAs suggested by the scalp EEG topography, the intracranial distribution of the human K-complex is maximal over the anterior and superior frontal cortices. K-complex generation appears limited to cortical regions above the inferior temporal sulcus laterally, the cingulate sulcus medially and the parietooccipital junction posteriorly.SignificanceThe human K-complex is produced by synchronous cortical activity that appears maximal intracranially over the superior medial and lateral aspects of the frontal lobes. The cingulate cortex and functionally related mesial temporal structures appear uninvolved in human K-complex generation.     

Neural correlates of spatial and nonspatial attention determined using intracranial electroencephalographic signals in humans

Few studies have directly compared the neural correlates of spatial attention (i.e., attention to a particular location) and nonspatial attention (i.e., attention to a feature in the visual scene) using well‐controlled tasks. Here, we investigated the neural correlates of spatial and nonspatial attention in humans using intracranial electroencephalography. The topography and number of electrodes showing significant event‐related desynchronization (ERD) or event‐related synchronization (ERS) in different frequency bands were studied in 13 epileptic patients. Performance was not significantly different between the two conditions. In both conditions, ERD in the low‐frequency bands and ERS in the high‐frequency bands were present bilaterally in the parietal cortex (prominently on the right hemisphere) and frontal regions. In addition to these common changes, spatial attention involved right‐lateralized activity that was maximal in the right superior parietal lobule (SPL), whereas nonspatial attention involved wider brain networks including the bilateral parietal, frontal, and temporal regions, but still had maximal activity in the right parietal lobe. Within the parietal lobe, spatial attention involved ERD or ERS in the right SPL, whereas nonspatial attention involved ERD or ERS in the right inferior parietal lobule. These findings reveal that common as well as different brain networks are engaged in spatial and nonspatial attention. Hum Brain Mapp 37:3041–3054, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Different localizations underlying cortical gelastic epilepsy: Case series and review of literature

BackgroundGelastic seizures (GS) are classically observed with hypothalamic hamartomas but they can also be associated with cortical epileptogenic foci.ObjectiveTo study the different cortical localizations associated with GS.MethodsWe reviewed the data from all patients with cortical GS investigated in our epilepsy unit from 1974 to 2012 and in the literature from 1956 to 2013.ResultsSixteen cases were identified in our database and 77 in the literature. Investigations provided confident focus localization in 9 and 18, respectively. In our series, the identified foci were located in the mesial temporal structures (2 left, 1 right), lateral temporal cortex (1 right), superior frontal gyrus (1 left), and operculoinsular region [3 right (orbitofrontal or frontal operculum extending into the anterior insula) and 1 left (frontal operculum extending into the anterior insula)]. In the literature, the identified foci (13 right/5 left) were located in the temporal lobe of 4 (1 right inferior, 1 right medial and inferior, 1 right posterior middle, inferior extending posteriorly to the lingual gyrus, and 1 left middle, inferior, and medial), in the frontal lobe of 12 [10 (6 right/4 left) medial (i.e., superior, medial frontal, and/or anterior cingulate gyri), 1 lateral (right anterior inferior frontal gyrus), and 1 right medioposterior orbitofrontal cortex] and in the parietal lobe of 2 (1 left superior parietal lobule and 1 right parietal operculum) patients.ConclusionIctal laughter is a poorly lateralizing and localizing feature as it may be encountered in patients with a focus in the left or right frontal, temporal, parietal, or insular lobe.     

Alpha-band cortico-cortical phase synchronization is associated with effective connectivity in the motor network

ObjectiveCommunication-through-coherence proposes that the phase synchronization (PS) of neural oscillations between cortical areas supports neural communication. In this study, we exploited transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) to test this hypothesis at the macroscale level, i.e., whether PS between cortical areas supports interarea communication. TEPs are electroencephalographic (EEG) responses time-locked to TMS pulses reflecting interarea communication, as they are generated by the transmission of neural activity from the stimulated area to connected regions. If interarea PS is important for communication, it should be associated with the TEP amplitude in the connected areas.MethodsTMS was delivered over the left primary motor cortex (M1) of fourteen healthy volunteers, and 70-channel EEG was recorded. Early TEP components were source-localized to identify their generators, i.e., distant brain regions activated by M1 through effective connections. Next, linear regressions were used to test the relationship between the TEP amplitude and the pre-stimulus PS between the M1 and the connected regions in four frequency bands (range 4–45 Hz).ResultsPre-stimulus interarea PS in the alpha-band was positively associated with the amplitude of early TEP components, namely, the N15 (ipsilateral supplementary motor area), P25 (contralateral M1) and P60 (ipsilateral parietal cortex).ConclusionsAlpha-band PS predicts the response amplitude of the distant brain regions effectively connected to M1.SignificanceOur study supports the role of EEG-PS in interarea communication, as theorized by communication-through-coherence.     

The neural basis of the P300 potential

Abstract. The locations and time-courses of the neural generators of the event-related P300 potential have been well described using intracranial recordings. However, this invasive method is not adequate for usage in healthy volunteers or psychiatric patients and not all brain regions can be covered well with this approach. With functional MRI, a non-invasive method with high spatial resolution, most of these locations could be found again. However, the time-course of these activations can only be roughly determined with this method, even if an event-related fMRI design has been chosen. Therefore, we have now tried to analyse the time-course of the activations using EEG data providing a better time resolution. We have used Low Resolution Electromagnetic Tomography (LORETA) in the analysis of P300 data (27 electrodes) of healthy volunteers (n = 50) in the time frame 230–480ms and found mainly the same activations that have been described using intracranial recordings or fMRI, i. e. the inferior patrietal lobe/temporo-parietal junction (TPJ), the supplementary motor cortex (SMA) and the anterior cingulate cortex (ACC), the superior temporal gyrus (STG), the insula and the dorsolateral prefrontal cortex. In these selected regions, an analysis of the activation time-courses has been performed.     

Cortical deactivations during gastric fundus distension in health: visceral pain‐specific response or attenuation of ‘default mode’ brain function? A H215O‐PET study

Abstract Gastric distension activates a cerebral network including brainstem, thalamus, insula, perigenual anterior cingulate, cerebellum, ventrolateral prefrontal cortex and potentially somatosensory regions. Cortical deactivations during gastric distension have hardly been reported. To describe brain areas of decreased activity during gastric fundus distension compared to baseline, using data from our previously published study (Gastroenterology, 128, 2005 and 564). H₂¹⁵O‐brain positron emission tomography was performed in 11 healthy volunteers during five conditions (random order): (C₁) no distension (baseline); isobaric distension to individual thresholds for (C₂) first, (C₃) marked, (C₄) unpleasant sensation and (C₅) sham distension. Subtraction analyses were performed (in SPM2) to determine deactivated areas during distension compared to baseline, with a threshold of P_{uncorrected_voxel_level} < 0.001 and P_{corrected_cluster_level} < 0.05. Baseline–maximal distension (C₁–C₄) yielded significant deactivations in: (i) bilateral occipital, lateral parietal and temporal cortex as well as medial parietal lobe (posterior cingulate and precuneus) and medial temporal lobe (hippocampus and amygdala), (ii) right dorsolateral and dorso‐ and ventromedial PFC, (iii) left subgenual ACC and bilateral caudate head. Intragastric pressure and epigastric sensation score correlated negatively with brain activity in similar regions. The right hippocampus/amygdala deactivation was specific to sham. Gastric fundus distension in health is associated with extensive cortical deactivations, besides the activations described before. Whether this represents task‐independent suspension of ‘default mode’ activity (as described in various cognitive tasks) or an visceral pain/interoception‐specific process remains to be elucidated.     

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

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

Differential functional brain network connectivity during visceral interoception as revealed by independent component analysis of fMRI time‐series

Influential theories of brain‐viscera interactions propose a central role for interoception in basic motivational and affective feeling states. Recent neuroimaging studies have underlined the insula, anterior cingulate, and ventral prefrontal cortices as the neural correlates of interoception. However, the relationships between these distributed brain regions remain unclear. In this study, we used spatial independent component analysis (ICA) and functional network connectivity (FNC) approaches to investigate time course correlations across the brain regions during visceral interoception. Functional magnetic resonance imaging (fMRI) was performed in thirteen healthy females who underwent viscerosensory stimulation of bladder as a representative internal organ at different prefill levels, i.e., no prefill, low prefill (100 ml saline), and high prefill (individually adapted to the sensations of persistent strong desire to void), and with different infusion temperatures, i.e., body warm (～37°C) or ice cold (4–8°C) saline solution. During Increased distention pressure on the viscera, the insula, striatum, anterior cingulate, ventromedial prefrontal cortex, amygdalo‐hippocampus, thalamus, brainstem, and cerebellar components showed increased activation. A second group of components encompassing the insula and anterior cingulate, dorsolateral prefrontal and posterior parietal cortices and temporal‐parietal junction showed increased activity with innocuous temperature stimulation of bladder mucosa. Significant differences in the FNC were found between the insula and amygdalo‐hippocampus, the insula and ventromedial prefrontal cortex, and the ventromedial prefrontal cortex and temporal‐parietal junction as the distention pressure on the viscera increased. These results provide new insight into the supraspinal processing of visceral interoception originating from an internal organ. Hum Brain Mapp 36:4438–4468, 2015. © 2015 Wiley Periodicals, Inc.     

GABA and cortical inhibition in motor and non-motor regions using combined TMS–EEG: A time analysis

ObjectiveThe induction of long interval cortical inhibition (LICI) in motor cortex with paired pulse transcranial magnetic stimulation (ppTMS) is an established paradigm for the assessment of cortical inhibition, proposed to be related to GABA_B receptor inhibitory neurotransmission. This study aimed to further evaluate recent methods of the assessment of LICI in non motor regions with ppTMS and electroencephalography (EEG).MethodsppTMS was applied using a single coil to the motor and dorsolateral prefrontal cortex (DLPFC) in 14 healthy subjects, and in the parietal lobe in 5 of those subjects.ResultsIn the motor cortex, LICI resulted in significant suppression in mean cortical evoked activity on EEG between 75 and 250 ms following delivery of the test stimulus. Maximal inhibition was seen from 50 to 250 ms in DLPFC, and between 50 and 175 ms in the parietal lobe.ConclusionsppTMS may be used to produce LICI in several cortical regions with a time course similar to known GABA_B activity.SignificanceppTMS induction of LICI can be recorded by combining TMS with EEG and seems to relate to GABA_B activity.     

The relationship between neuropsychological tests of visuospatial function and lobar cortical thickness

Introduction: Tests of visuospatial function are often administered in comprehensive neuropsychological evaluations. These tests are generally considered assays of parietal lobe function; however, the neural correlates of these tests, using modern imaging techniques, are not well understood. In the current study we investigated the relationship between three commonly used tests of visuospatial function and lobar cortical thickness in each hemisphere.

Method: Data from 374 patients who underwent a neuropsychological evaluation and MRI scans in an outpatient dementia clinic were included in the analysis. We examined the relationships between cortical thickness, as assessed with Freesurfer, and performance on three tests: Judgment of Line Orientation (JoLO), Block Design (BD) from the Fourth edition of the Wechsler Adult Intelligence Scale, and Brief Visuospatial Memory Test-Revised Copy Trial (BVMT–R-C) in patients who showed overall average performance on these tasks. Using a series of multiple regression models, we assessed which lobe’s overall cortical thickness best predicted test performance.

Results: Among the individual lobes, JoLO performance was best predicted by cortical thickness in the right temporal lobe. BD performance was best predicted by cortical thickness in the right parietal lobe, and BVMT–R-C performance was best predicted by cortical thickness in the left parietal lobe.

Conclusions: Performance on constructional tests of visuospatial function appears to correspond best with underlying cortical thickness of the parietal lobes, while performance on visuospatial judgment tests appears to correspond best to temporal lobe thickness. Future research using voxel-wise and connectivity techniques and including more diverse samples will help further understanding of the regions and networks involved in visuospatial tests.     

Top-down and bottom-up attention to memory: a hypothesis (AtoM) on the role of the posterior parietal cortex in memory retrieval

Recent neuroimaging studies have implicated the posterior parietal cortex in episodic memory retrieval, but there is uncertainty about its specific role. Research in the attentional domain has shown that superior parietal lobe (SPL) regions along the intraparietal sulcus are implicated in the voluntary orienting of attention to relevant aspects of the environment, whereas inferior parietal lobe (IPL) regions at the temporo-parietal junction mediate the automatic allocation of attention to task-relevant information. Here we propose that the SPL and the IPL play conceptually similar roles in episodic memory retrieval. We hypothesize that the SPL allocates top-down attention to memory retrieval, whereas the IPL mediates the automatic, bottom-up attentional capture by retrieved memory contents. By reviewing the existing fMRI literature, we show that the posterior intraparietal sulcus of SPL is consistently active when the need for top-down assistance to memory retrieval is supposedly maximal, e.g., for memories retrieved with low vs. high confidence, for familiar vs. recollected memories, for recognition of high vs. low frequency words. On the other hand, the supramarginal gyrus of IPL is consistently active when the attentional capture by memory contents is supposedly maximal, i.e., for strong vs. weak memories, for vividly recollected vs. familiar memories, for memories retrieved with high vs. low confidence. We introduce a model of episodic memory retrieval that characterizes contributions of posterior parietal cortex.     

Anatomical and fMRI-network comparison of multiple DLPFC targeting strategies for repetitive transcranial magnetic stimulation treatment of depression

BackgroundThe efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression may vary depending on the subregion stimulated within the dorsolateral prefrontal cortex (DLPFC). Clinical TMS typically uses scalp-based landmarks for DLPFC targeting, rather than individualized MRI guidance.ObjectiveIn rTMS patients, determine the brain systems targeted by multiple DLPFC stimulation rules by computing several surrogate measures: underlying brain targets labeled with connectivity-based atlases, subgenual cingulate anticorrelation strength, and functionally connected networks.MethodsForty-nine patients in a randomized controlled trial of rTMS therapy for treatment resistant major depression underwent structural and functional MRI. DLPFC rules were applied virtually using MR-image guidance. Underlying cortical regions were labeled, and connectivity with the subgenual cingulate and whole-brain computed.ResultsScalp-targeting rules applied post hoc to these MRIs that adjusted for head size, including Beam F3, were comparably precise, successful in directly targeting classical DLPFC and frontal networks, and anticorrelated with the subgenual cingulate. In contrast, all rules involving fixed distances introduced variability in regions and networks targeted. The 5 cm rule targeted a transitional DLPFC region with a different connectivity profile from the adjusted rules. Seed-based connectivity analyses identified multiple regions, such as posterior cingulate and inferior parietal lobe, that warrant further study in order to understand their potential contribution to clinical response.ConclusionEEG-based rules consistently targeted DLPFC brain regions with resting-state fMRI features known to be associated with depression response. These results provide a bridge from lab to clinic by enabling clinicians to relate scalp-targeting rules to functionally connected brain systems.     

Amnestic mild cognitive impairment in Parkinson's disease: A brain perfusion SPECT study

The purpose of this study was to investigate cortical dysfunction in Parkinson's disease (PD) patients with amnestic deficit (PD‐MCI). Perfusion single photon emission computed tomography was performed in 15 PD‐MCI patients and compared (statistical parametric mapping [SPM2]) with three groups, i.e., healthy subjects (CTR), cognitively intact PD patients (PD), and common amnestic MCI patients (aMCI). Age, depression, and UPDRS‐III scores were considered as confounding variables. PD‐MCI group (P < 0.05, false discovery rate–corrected for multiple comparisons) showed relative hypoperfusion in bilateral posterior parietal lobe and in right occipital lobe in comparison to CTR. As compared to aMCI, MCI‐PD demonstrated hypoperfusion in bilateral posterior parietal and occipital areas, mainly right cuneus and angular gyrus, and left precuneus and middle occipital gyrus. With a less conservative threshold (uncorrected P < 0.01), MCI‐PD showed hypoperfusion in a left parietal region, mainly including precuneus and inferior parietal lobule, and in a right temporal‐parietal‐occipital region, including middle occipital and superior temporal gyri, and cuneus‐precuneus, as compared to PD. aMCI versus PD‐MCI showed hypoperfusion in bilateral medial temporal lobe, anterior cingulate, and left orbitofrontal cortex. PD‐MCI patients with amnestic deficit showed cortical dysfunction in bilateral posterior parietal and occipital lobes, a pattern that can be especially recognized versus both controls and common aMCI patients, and to a lesser extent versus cognitively intact PD. The relevance of this pattern in predicting dementia should be evaluated in longitudinal studies. © 2008 Movement Disorder Society     

Functional connectivity corresponding to the tonotopic differentiation of the human auditory cortex

Recent research has demonstrated that resting‐state functional connectivity (RS‐FC) within the human auditory cortex (HAC) is frequency‐selective, but whether RS‐FC between the HAC and other brain areas is differentiated by frequency remains unclear. Three types of data were collected in this study, including resting‐state functional magnetic resonance imaging (fMRI) data, task‐based fMRI data using six pure tone stimuli (200, 400, 800, 1,600, 3,200, and 6,400 Hz), and structural imaging data. We first used task‐based fMRI to identify frequency‐selective cortical regions in the HAC. Six regions of interest (ROIs) were defined based on the responses of 50 participants to the six pure tone stimuli. Then, these ROIs were used as seeds to determine RS‐FC between the HAC and other brain regions. The results showed that there was RS‐FC between the HAC and brain regions that included the superior temporal gyrus, dorsolateral prefrontal cortex (DL‐PFC), parietal cortex, occipital lobe, and subcortical structures. Importantly, significant differences in FC were observed among most of the brain regions that showed RS‐FC with the HAC. Specifically, there was stronger RS‐FC between (1) low‐frequency (200 and 400 Hz) regions and brain regions including the premotor cortex, somatosensory/‐association cortex, and DL‐PFC; (2) intermediate‐frequency (800 and 1,600 Hz) regions and brain regions including the anterior/posterior superior temporal sulcus, supramarginal gyrus, and inferior frontal cortex; (3) intermediate/low‐frequency regions and vision‐related regions; (4) high‐frequency (3,200 and 6,400 Hz) regions and the anterior cingulate cortex or left DL‐PFC. These findings demonstrate that RS‐FC between the HAC and other brain areas is frequency selective.     

Functional correlates of vertical gaze palsy and other ocular motor deficits in PSP: An FDG-PET study

ObjectiveTo determine the functional correlates of vertical gaze palsy and other ocular motor deficits in patients with progressive supranuclear palsy (PSP) using [¹⁸F]fluorodeoxyglucose (FDG-)PET.MethodsTwenty-six patients with PSP underwent clinical examination of vertical gaze combined with FDG-PET scans to assess regional cerebral glucose metabolism as a marker of neuronal activity. Of these, eighteen PSP patients were also investigated by electrical nystagmography to determine horizontal ocular motor deficits. Statistical parametric mapping analyses were performed to correlate regional neuronal activity with ocular motor functions.ResultsIn categorical comparisons, patients with downward gaze palsy showed a significantly reduced glucose metabolism in bilateral anterior cingulate gyrus and right lingual gyrus compared to those without downward gaze palsy. Maximum velocity of horizontal saccades was positively correlated with glucose metabolism of the rostral vermis and lingual gyrus; regional metabolism of oculomotor vermis was associated with peak velocity of the optokinetic reflex. Analysis of smooth pursuit eye movement amplitude and peak velocity of corrective saccades showed positive correlation with metabolism in bilateral inferior parietal lobe and inferior part of the frontal eye field. All paradigms of smooth pursuit showed positive association with glucose metabolism in V5.ConclusionsOcular motor functions in PSP are correlated with neuronal activity in distinct anatomical regions. These include the anterior cingulate gyrus (downward gaze palsy), rostral cerebellum (saccades), oculomotor vermis (optokinetic reflex) and inferior parietal as well as temporal regions and frontal eye field (smooth pursuit). These findings provide a deeper insight into the pathophysiology of PSP-associated ocular motor abnormalities.     

Temporal discounting for self and friends in adolescence: A fMRI study

Adolescence is characterized by impulsivity but also by increased importance of friendships. This study took the novel perspective of testing temporal discounting in a fMRI task where choices could affect outcomes for 96 adolescents (aged 10–20-years) themselves and their best friend. Decisions either benefitted themselves (i.e., the Self Immediate – Self Delay’ condition) or their friend (i.e., ‘Friend Immediate – Friend Delay’ condition); or juxtaposed rewards for themselves and their friends (i.e., the ‘Self Immediate – Friend Delay’ or ‘Friend Immediate – Self Delay’ conditions). We observed that younger adolescents were more impulsive; and all participants were more impulsive when this was associated with an immediate benefit for friends. Individual differences analyses revealed increased activity in the subgenual anterior cingulate cortex extending in the ventral striatum for immediate relative to delayed reward choices for self. Temporal choices were associated with activity in the prefrontal cortex, parietal cortex, insula, and ventral striatum, but only activity in the right inferior parietal lobe was associated with age. Finally, temporal delay choices for friends relative to self were associated with increased activity in the temporo-parietal junction and precuneus. Overall, this study shows a unique role of the social context in adolescents’ temporal decision making.     

Priming words with pictures: Neural correlates of semantic associations in a cross‐modal priming task using fMRI

In our everyday life we process information from different modalities simultaneously with great ease. With the current study we had the following goals: to detect the neural correlates of (1) automatic semantic processing of associates and (2) to investigate the influence of different visual modalities on semantic processing. Stimuli were presented with a short SOA (350 ms) as subjects performed a lexical decision task. To minimize the variance and increase homogeneity within our sample, only male subjects were measured. Three experimental conditions were compared while brain activation was measured with a 3 T fMRI scanner: related word‐pairs (e.g., frame–picture), unrelated word‐pairs (e.g., frame–car) as well as word‐nonword pairs (e.g., frame–fubber). They were presented uni‐ (word ‐word) and cross‐modally (picture–word). Behavioral data revealed a priming effect for cross‐modal and unimodal word‐pairs. On a neural level, the unimodal condition revealed response suppression in bilateral fronto‐parietal regions. Cross‐modal priming led to response suppression within the right inferior frontal gyrus. Common areas of deactivation for both modalities were found in bilateral fronto‐tempo‐parietal regions. These results suggest that the processing of semantic associations presented in different modalities lead to modality‐specific activation caused by early access routes. However, common activation for both modalities refers to a common neural network for semantic processing suggesting amodal processing. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Inefficiently increased anterior cingulate modulation of cortical systems during working memory in young offspring of schizophrenia patients

Background

Children and adolescent offspring of schizophrenia patients are at increased risk for schizophrenia and are also characterized by impairments in brain structure and function. To date, few studies have investigated whether functional interactions between brain regions are intact or altered. Using an established verbal working memory paradigm with variable levels of memory load, we investigated the modulatory effect of activity in cognitive control regions of the brain (specifically the dorsal anterior cingulate cortex) on activity in core working memory regions, in particular the dorsal prefrontal cortex and the parietal lobe.

Methods

Forty four subjects participated. An n-back task with two levels of working memory load (1- and 2-back) was employed during fMRI (4 T Bruker MedSpec system). Data were processed with SPM5 and the modulatory effects of the anterior cingulate were investigated using psycho-physiological interaction (PPI).

Results

In spite of only subtle activation differences, and no significant differences in performance accuracy, a significant group x memory load interaction in the parietal lobe, indicated aberrantly increased modulatory inputs to this region under conditions of high working memory load in schizophrenia offspring.

Discussion

Increased modulatory inputs from a central control region like the anterior cingulate presumably reflect relative inefficiency in intra-cortical interactions in the vulnerable brain. This inefficiency may reflect a developmentally mediated impairment in functional brain interactions in this important vulnerable population. It is highly plausible that the resultant effect of these altered interactions is an increased vulnerability to impaired brain development, and therefore to psychiatric disorders including schizophrenia.     

Correlation of regional cerebral blood flow equivalents measured by single photon emission computerized tomography with P300 latency and eye movement abnormality in schizophrenia

Single photon emission tomography with the intravenous blood flow marker ^99mTc-exametazime was carried out in 14 acutely ill drug-free schizophrenic patients from whom P300 event-related potential, smooth eye pursuit eye tracking and verbal fluency were measured within a few days of scanning. Smooth pursuit eye movement abnormality correlated significantly with abnormal tracer uptake in superior pre-frontal cortex on the right and left and inferior pre-frontal cortex on the left. Abnormal eye movement was also associated with higher tracer uptake in left anterior cingulate and left posterior cingulate. P300 latency was significantly correlated with higher tracer uptake in left superior pre-frontal and left parietal regions. Verbal fluency performance was negatively correlated with tracer uptake in left frontal region. Eye tracking abnormality in schizophrenia is associated with bilateral frontal lobe disturbance and P300 latency increase with left-sided frontal and temporoparietal dysfunction. There was, however, a significant inverse relation between eye tracking abnormalities and abnormal perfusion in the left anterior cingulate region.     

Modifications of cognitive and motor tasks affect the occurrence of event-related potentials in the human cortex

This study concerns the question of how task modification affects the frequency occurrence of event-related potentials (ERP) inside the active cortical areas. In 13 candidates for epilepsy surgery, 156 sites in the temporal (74), frontal (73), and parietal (9) cortices were recorded by means of depth and subdural electrodes. Four modifications of the somatosensory evoked P3-like potentials were performed; (i) an oddball paradigm with silent counting of target stimuli (P3c); (ii) an oddball paradigm with a hand movement in response to target stimuli (P3m); (iii) an S1-S2 paradigm, ERP in the P300 time window after the S2 stimulus, with silent counting of target stimuli (S2c), and (iv) an S1-S2 paradigm with a hand movement in response to target stimuli (S2m). In comparing the oddball paradigms with the S1-S2 (contingent negative variation, CNV) paradigms, four regions emerge that are significantly linked with the oddball P3; the prefrontal cortex, the cingulate, the amygdalo-hippocampal complex, and the lateral temporal cortex. A prominent role of the cingulate and the fronto-orbital cortex in the cognitive processing of movement was supported when tasks with identical cognitive loads but different required responses were compared. Even relatively simple cognitive tasks activate many cortical regions. The investigated areas were activated in all tests; however, small regions in each field were active or inactive in relation to the nature of the task. The study indicates a variable and task-dependent internal organization of a highly complex and widely distributed system of active cortical areas.