Neural activity in the hippocampus predicts individual visual short‐term memory capacity

Although the hippocampus had been traditionally thought to be exclusively involved in long‐term memory, recent studies raised controversial explanations why hippocampal activity emerged during short‐term memory tasks. For example, it has been argued that long‐term memory processes might contribute to performance within a short‐term memory paradigm when memory capacity has been exceeded. It is still unclear, though, whether neural activity in the hippocampus predicts visual short‐term memory (VSTM) performance. To investigate this question, we measured BOLD activity in 21 healthy adults (age range 19–27 yr, nine males) while they performed a match‐to‐sample task requiring processing of object‐location associations (delay period = 900 ms; set size conditions 1, 2, 4, and 6). Based on individual memory capacity (estimated by Cowan's K‐formula), two performance groups were formed (high and low performers). Within whole brain analyses, we found a robust main effect of “set size” in the posterior parietal cortex (PPC). In line with a “set size × group” interaction in the hippocampus, a subsequent Finite Impulse Response (FIR) analysis revealed divergent hippocampal activation patterns between performance groups: Low performers (mean capacity = 3.63) elicited increased neural activity at set size two, followed by a drop in activity at set sizes four and six, whereas high performers (mean capacity = 5.19) showed an incremental activity increase with larger set size (maximal activation at set size six). Our data demonstrated that performance‐related neural activity in the hippocampus emerged below capacity limit. In conclusion, we suggest that hippocampal activity reflected successful processing of object‐location associations in VSTM. Neural activity in the PPC might have been involved in attentional updating. © 2013 Wiley Periodicals, Inc.     

Objective PET study of glucose metabolism asymmetries in children with epilepsy: Implications for normal brain development

Clinical interpretation of cerebral positron emission tomography with 2‐deoxy‐2[F‐18]fluoro‐d ‐glucose (FDG‐PET) images often relies on evaluation of regional asymmetries. This study was designed to establish age‐related variations in regional cortical glucose metabolism asymmetries in the developing human brain. FDG‐PET scans of 58 children (age: 1–18 years) were selected from a large single‐center pediatric PET database. All children had a history of epilepsy, normal MRI, and normal pattern of glucose metabolism on visual evaluation. PET images were analyzed objectively by statistical parametric mapping with the use of age‐specific FDG‐PET templates. Regional FDG uptake was measured in 35 cortical regions in both hemispheres using an automated anatomical labeling atlas, and left/right ratios were correlated with age, gender, and epilepsy variables. Cortical glucose metabolism was mostly symmetric in young children and became increasingly asymmetric in older subjects. Specifically, several frontal cortical regions showed an age‐related increase of left > right asymmetries (mean: up to 10%), while right > left asymmetries emerged in posterior cortex (including portions of the occipital, parietal, and temporal lobe) in older children (up to 9%). Similar trends were seen in a subgroup of 39 children with known right‐handedness. Age‐related correlations of regional metabolic asymmetries showed no robust gender differences and were not affected by epilepsy variables. These data demonstrate a region‐specific emergence of cortical metabolic asymmetries between age 1–18 years, with left > right asymmetry in frontal and right > left asymmetry in posterior regions. The findings can facilitate correct interpretation of cortical regional asymmetries on pediatric FDG‐PET images across a wide age range.     

Positron emission tomography imaging in gliomas: applications in clinical diagnosis,for assessment of prognosis and of treatment effects,and for detection of recurrences

Neuroimaging plays a significant role in the diagnosis of intracranial tumours, especially brain gliomas, and must consist of an assessment of location and extent of the tumour and of its biological activity. Therefore, morphological imaging modalities and functional, metabolic or molecular imaging modalities should be combined for primary diagnosis and for following the course and evaluating therapeutic effects. Magnetic resonance imaging (MRI) is the gold standard for providing detailed morphological information and can supply some additional insights into metabolism (MR spectroscopy) and perfusion (perfusion‐weighted imaging) but still has limitations in identifying tumour grade, invasive growth into neighbouring tissue and treatment‐induced changes, as well as recurrences. These insights can be obtained by various positron emission tomography (PET) modalities, including imaging of glucose metabolism, amino acid uptake and nucleoside uptake. Diagnostic accuracy can benefit from coregistration of PET results and MRI, combining high‐resolution morphological images with biological information. These procedures are optimized by the newly developed combination of PET and MRI modalities, permitting the simultaneous assessment of morphological, functional, metabolic and molecular information on the human brain.     

Representations of Graphomotor Trajectories in the Human Parietal Cortex: Evidence for Controlled Processing and Automatic Performance

The aim of this study was to identify the cerebral areas activated during kinematic processing of movement trajectories. We measured regional cerebral blood flow (rCBF) during learning, performance and imagery of right-hand writing in eight right-handed volunteers. Compared with viewing the writing space, increases in rCBF were observed in the left motor, premotor and frontomesial cortex, and in the right anterior cerebellum in all movement conditions, and the increases were related to mean tangential writing velocity. No rCBF increases occurred in these areas during imagery. Early learning of new ideomotor trajectories and deliberately exact writing of letters both induced rCBF increases in the cortex lining the right intraparietal sulcus. In contrast, during fast writing of overlearned trajectories and in the later phase of learning new ideograms the rCBF increased bilaterally in the posterior parietal cortex. Imagery of ideograms that had not been practised previously activated the anterior and posterior parietal areas simultaneously. Our results provide evidence suggesting that the kinematic representations of graphomotor trajectories are multiply represented in the human parietal cortex. It is concluded that different parietal subsystems may subserve attentive sensory movement control and whole-field visuospatial processing during automatic performance.     

Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia

The posterior cingulate cortex (PCC), a key component of the limbic system, has been implicated in the pathology of schizophrenia because of its sensitivity to NMDA receptor antagonists. Recent studies have shown that the PCC is dysfunctional in schizophrenia, and it is now suspected to be critically involved in the pathogenesis of schizophrenia. Studies also suggest that there are abnormalities in muscarinic and GABAergic neurotransmission in schizophrenia. Therefore, in the present study we used quantitative autoradiography to investigate the binding of [(3)H]pirenzepine, [(3)H]AF-DX 384 and [(3)H]muscimol, which respectively label M1/4 and M2/4 muscarinic and GABA(A) receptors, in the PCC of schizophrenia and control subjects matched for age and post-mortem interval. The present study found that [(3)H]pirenzepine binding was significantly decreased in the superficial (-24%, p=0.002) and deep (-35%, p<0.001) layers of the PCC in the schizophrenia group as compared with the control group. In contrast, a dramatic increase in [(3)H]muscimol binding was observed in the superficial (+112%, p=0.001) and deep layers (+100%, p=0.017) of the PCC in the schizophrenia group. No difference was observed for [(3)H]AF-DX 384 binding between the schizophrenia and control groups. The authors found a significant inverse correlation between [(3)H]pirenzepine binding in the deep cortical layers and [(3)H]muscimol binding in the superficial layers (rho=-0.732, p=0.003). In addition, negative correlations were also found between age and [(3)H]pirenzepine binding in both superficial and deep cortical layers (rho=-0.669 p=0.049 and rho=-0.778, p=0.014), and between age of schizophrenia onset and [(3)H]AF-DX 384 binding (rho=-0.798, p=0.018). These results for the first time demonstrated the status of M1/M4, M2/M4 and GABA(A) receptors in the PCC in schizophrenia. Whilst the exact mechanism causing these alterations is not yet known, a possible increased acetylcholine and down regulated GABA stimulation in the PCC of schizophrenia is suggested.     

High-frequency rTMS treatment increases left prefrontal myo-inositol in young patients with treatment-resistant depression

Background

Neuroimaging studies suggest that the prefrontal cortex (PFC) is involved in the pathophysiology of major depression. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. In this study metabolic changes within PFC of severely depressed patients before and after rTMS were evaluated by proton magnetic resonance spectroscopy (1H-MRS).

Method

Thirty-four young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study〔active ((n = 19) vs. sham(n = 15)), and the PFC was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy. Response was defined as a 50% reduction of the Hamilton depression rating scale. The results were compared with 28 age- and gender-matched healthy controls.

Results

In depressive patients a significant reduction in myo-inositol (m-Ino) was observed pre-rTMS (p < 0.001). After successful treatment, m-Ino increased significantly in left PFC and the levels no longer differed from those of age-matched controls. In addition to a positive correlation between clinical improvement and an increment in m-Ino ratio, a correlation between clinical improvement and early age onset was observed.

Conclusions

Our results support the notion that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in myo-inositol metabolism, which can be partly reversed by successful rTMS.     

Delusional infestation: Neural correlates and antipsychotic therapy investigated by multimodal neuroimaging

Introduction

In delusional infestation (DI), as with other non-schizophrenic psychotic disorders, little is known about the neural basis and the mechanisms of antipsychotic treatment. We aimed at investigating the brain circuitry involved in DI and the role of postsynaptic D2 receptors in mediating the effects of antipsychotics by means of multimodal neuroimaging.

Methods

In Case 1, a patient with DI (initially drug-induced), cerebral glucose metabolism and dopaminergic neurotransmission were studied in the untreated state (FDG-PET, FDOPA-PET, 123I-FP-CIT-SPECT, and IBZM-SPECT) and after effective aripiprazole treatment (FDG-PET and IBZM-SPECT), with negative drug screenings at both imaging sessions. In Case 2 (DI secondary to mild vascular encephalopathy) cerebral perfusion and gray matter volume changes were investigated in the untreated state and compared to N = 7 age-matched healthy controls (MRI-based CASL and VBM).

Results

In Case 1, before treatment, glucose metabolism was left-dominant in the thalamus and the putamen. Pre- and postsynaptic dopaminergic neurotransmissions were altered in the striatum, again mainly the left putamen. Full remission to aripiprazole was associated with 63 to 78% striatal D2 receptor occupancy and glucose metabolism changes in the bilateral thalamus. In Case 2, significant perfusion and GMV changes were observed in the bilateral putamen, frontal and parietal somatosensory cortices as compared to controls. Symptoms partially remitted to ziprasidone therapy.

Discussion/conclusion

Six imaging techniques were first used to study the neural basis of DI and mechanisms of antipsychotic therapy. The study provides first low-level evidence in vivo evidence of fronto-striato-thalamo-parietal network to mediate core symptoms of DI, i.e. a priori brain regions involved in judgment (frontal cortex), sensory gating (thalamus) and body perception (dorsal striatum, thalamus and somatic cortices). This is also the first report of effective treatment with aripiprazole in drug-induced DI and with ziprasidone in organic DI, adding to existing limited evidence that SGAs are helpful in various forms of DI. Effective antipsychotic treatment seems to depend on blocking striatal D2 receptors with similar occupancy rates as in schizophrenia. Larger samples are needed to confirm our preliminary findings and further evaluate their relevance for the different forms of DI.     

Schneiderian first rank symptoms and inferior parietal lobule cortical thickness in antipsychotic-naïve schizophrenia

Inferior parietal lobule (IPL) is implicated in the pathogenesis of first rank symptoms (FRS) in schizophrenia by functional neuroimaging studies. However, the relationship between IPL cortical thickness and FRS is yet to be explored. In this study, cortical thickness of IPL was analyzed in antipsychotic-naïve schizophrenia patients (total number = 51) with [FRS(+); N = 25] and those without FRS [FRS(−); N = 26] in comparison with group-matched healthy controls (N = 47). FRS(+) patients showed significant cortical thickness deficit in right IPL (specifically angular gyrus) in comparison with both FRS(−) patients (p = 0.005) and healthy controls (p = 0.0002); lack of difference on the left side might possibly be related to larger variance in healthy controls. Deficient cortical thickness involving IPL in FRS(+) schizophrenia patients adds further support to the role of internal monitoring system in the pathogenesis of FRS in schizophrenia.     

Profiles of DARPP-32 in the insular cortex with schizophrenia: a postmortem brain study

In patients with schizophrenia, various physical disorders are sometimes discovered only when they have reached a later and more severe stage. This phenomenon is believed to be caused, at least in part, by an increase in pain threshold. The gamma-aminobutyric acid (GABA)-ergic and glutamatergic systems in the rostral agranular insular cortex (RAIC) are thought to be involved in the regulation of pain threshold. However, no postmortem studies of the cerebral cortex have previously been published. Dopamine and cAMP-regulated phosphoprotein 32 kD (DARPP-32), which is involved in the GABAergic and glutamatergic systems, is considered to be crucial for elucidating the pathogenesis of schizophrenia.Using specific antibodies, we conducted immunohistochemical examinations of the RAIC in 10 subjects from a healthy control group, and 11 subjects from a schizophrenia group. The sex, age, and postmortem interval (PMI) of the schizophrenia group were matched to those of the healthy control group. We revealed that the density of DARPP-32-immunoreactive (IR) neurons in the II and III layers of the RAIC was significantly decreased (p < 0.05) in the schizophrenia group compared with the healthy control group. Our findings could partially explain the molecular basis of the pain threshold abnormalities found in patients with schizophrenia.     

Abnormal regional spontaneous neural activity in first-episode,treatment-naive patients with late-life depression: A resting-state fMRI study

Background

The previous resting perfusion or task-based studies have provided evidence of functional changes in the brains of patients with late-life depression (LLD). Little is known, so far, about the changes in the spontaneous brain activity in LLD during the resting state. The aim of this study was to investigate the spontaneous neural activity in first-episode, treatment-naive patients with LLD by using resting-state functional magnetic resonance imaging (fMRI).

Methods

A novel analytical method, coherence-based regional homogeneity (Cohe-ReHo), was used to assess regional spontaneous neural activity during the resting state in 15 first-episode, treatment-naive patients with LLD and 15 age- and gender-matched healthy controls.

Results

Compared to the healthy controls, the LLD group showed significantly decreased Cohe-ReHo in left caudate nucleus, right anterior cingulate gyrus, left dorsolateral prefrontal cortex, right angular gyrus, bilateral medial prefrontal cortex, and right precuneus, while significantly increased Cohe-ReHo in left cerebellum posterior lobe, left superior temporal gyrus, bilateral supplementary motor area, and right postcentral gyrus (p < 0.005, corrected for multiple comparisons).

Conclusions

These findings indicated abnormal spontaneous neural activity was distributed extensively in first-episode, treatment-naive patients with LLD during the resting state. Our results might supply a novel way to look into the underlying pathophysiology mechanisms of patients with LLD.     

Neuroimaging in social anxiety disorder: A systematic review of the literature

Brain imaging techniques allow the in vivo evaluation of the human brain, leading to a better understanding of its anatomical, functional and metabolic substrate. The aim of this current report is to present a systematic and critical review of neuroimaging findings in Social Anxiety Disorder (SAD). A literature review was performed in the PubMed Medline, Scielo and Web of Science databases using the following keywords: ‘MRI’, ‘functional’, ‘tomography’, ‘PET’, ‘SPECT’, ‘spectroscopy’, ‘relaxometry’, ‘tractography’ and ‘voxel’ crossed one by one with the terms ‘social anxiety’ and ‘social phobic’, with no limit of time. We selected 196 articles and 48 of them were included in our review. Most of the included studies have explored the neural response to facial expressions of emotion, symptoms provocation paradigms, and disorder-related abnormalities in dopamine or serotonin neurotransmission. The most coherent finding among the brain imaging techniques reflects increased activity in limbic and paralimbic regions in SAD. The predominance of evidence implicating the amygdala strengthens the notion that it plays a crucial role in the pathophysiology of SAD. The observation of alterations in pre-frontal regions and the reduced activity observed in striatal and parietal areas show that much remains to be investigated within the complexity of SAD. Interesting, follow-up designed studies observed a decrease in perfusion in these same areas after either by pharmacological or psychological treatment. The medial prefrontal cortex provided additional support for a corticolimbic model of SAD pathophysiology, being a promising area to investigation. Furthermore, the dopaminergic and GABAergic hypotheses seem directed related to its physiopathology. The present review indicates that neuroimaging has contributed to a better understanding of the neurobiology of SAD. Although there were several methodological differences among the studies, the global results have often been consistent, reinforcing the evidence of a specific cerebral circuit involved in SAD, formed by limbic and cortical areas.     

Auditory orienting and inhibition of return in schizophrenia: A functional magnetic resonance imaging study

Background

The brain mechanisms of cognitive-behavioral therapy (CBT), a highly effective treatment for pediatric obsessive-compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging (¹H MRSI).

Method

Five unmedicated OCD patients (4 ♀, 13.5 ± 2.8) and 9 healthy controls (7 ♀, 13.0 ± 2.5) underwent MRSI (1.5 T, repetition-time/echo-time = 1500/30 ms) of bilateral putamen, thalamus and pregenual anterior cingulate cortex (pACC). Patients were rescanned after 12 weeks of exposure-based CBT. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) of OCD symptoms was administered before and after CBT.

Results

Four of 5 patients responded to CBT (mean 32.8% CY-BOCS reduction). Multiple metabolite effects emerged. Pre-CBT, N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA) in left pregenual anterior cingulate cortex (pACC) was 55.5% higher in patients than controls. Post-CBT, tNAA (15.0%) and Cr (23.9%) in left pACC decreased and choline compounds (Cho) in right thalamus increased (10.6%) in all 5 patients. In left thalamus, lower pre-CBT tNAA, glutamate + glutamine (Glx), and myo-inositol (mI) predicted greater post-CBT drop in CY-BOCS (r = 0.98) and CY-BOCS decrease correlated with increased Cho.

Conclusions

Interpretations are offered in terms of the Glutamatergic Hypothesis of Pediatric OCD. Similar to ¹⁸FDG-PET in adults, objectively measurable regional MRSI metabolites may indicate pediatric OCD and predict its response to CBT.     

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group

The analysis of spontaneous EEG activity and evoked potentials is a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). The past few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury, opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of both consolidated and investigational electrophysiological techniques for the prognostic and diagnostic assessment of DoC. We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats. The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.