The relationship between brain structure and neurocognition in schizophrenia: a selective review

Both Kraepelin [1919. Dementia Praecox and Paraphrenia, Livingston, Edinburgh.] and Bleuler [1911. Dementia Praecox or the Group of Schizophrenias. Reprinted 1950 (trans. and ed. J. Zinkin). New York: International Univ. Press.] proposed that cognitive disturbances in schizophrenia are manifestations of brain abnormality. With the advent of magnetic resonance imaging (MRI) methodology, a number of studies have attempted to determine the relationship between brain structure and neurocognition in schizophrenia. We performed a review (1991–to date) of such studies with the aim of identifying the most consistent and compelling findings. The review revealed that whole brain volume tends to correlate with the measures of general intelligence as well as with a range of specific cognitive functions in normal controls and female schizophrenia patients, but this relationship is disrupted in male patients. The enlargement of the third ventricle, relative to the whole brain volume, is associated with deficient abstraction/flexibility, language, and attention/concentration in patients, whereas disproportionally larger lateral ventricles are associated with poorer psychomotor speed and attention/concentration in women, but not in men, with schizophrenia. Archicortical, but not paleocortical, prefrontal cortex tends to associate with the measures of executive function in both sexes regardless of diagnosis. Temporal lobe, hippocampus and parahippocampal gyrus correlate with cognitive abilities such as performance speed and accuracy, memory and executive function, verbal endowment and abstraction/categorization, respectively. Some of these medial temporal lobe/neurocognition relationships appear to be specific to schizophrenia (i.e. not seen in controls). Striatal size is positively associated with goal-directed behavior, but not perseveration, in schizophrenia. Larger cerebellum is associated with higher IQ in normal controls and affected women, but this association is disrupted in affected men. Increased white matter of the vermis is associated with poorer language and immediate verbal memory in schizophrenia. Finally, the methodological limitations of the reviewed studies are discussed and suggestions for future research are offered.     

创伤后应激障碍的认知功能与脑血流情况研究

目的 探讨创伤后应激障碍患者的认知功能状况、脑血流情况及其之间的关系.方法 对100例创伤后应激障碍患者进行听觉事件相关诱发电位（P300）检查以评价其认知功能.对认知功能＂差＂和＂极差＂的患者进行多普勒脑血流图TCD检查,记录血流峰值及脉动指数,以评价其脑血流情况.结果 100例创伤后应激障碍患者P300检查中,84例认知功能为＂差＂和＂极差＂,该84例患者TCD检查结果显示：大脑中动脉和大脑前动脉的动脉指数均高于我国正常成人常模,差异有显著性.结论 多数创伤后应激障碍者的认知功能出现障碍,可能与其大脑中动脉、大脑前动脉血管收缩调节功能下降导致大脑前额叶供血不足有关.     

镜像书写与大脑功能关系的探讨

本文检测了学龄前儿童72名,学龄儿童40名和弱智学龄儿童60名的镜像书写情况。检查结果表明学龄前儿童组、学龄儿童组和弱智学龄儿童组用左手书写时镜像书写的出现率分别为45.8％、10％和43.3％;定向力差者分别为47.2％、22.5％和41.7％。弱智学龄儿童中镜像书写出现率较高是因智力落后使书写运动一图式和镜像书写运动一图式在两侧大脑半球建立得不够牢固有关。所以是否可考虑镜像书写归为儿童智力测定的项目之     

脑的神奇结构--海马与复杂部分性癫痫的密切联系

海马与复杂部分性癫痫的发生及形成之间的密切关系已为人们所熟知,这有赖于近年对其结构的深入认识,更有赖于在明确解剖结构的基础上,对其功能的进一步了解。     

Goal-striving tendencies moderate the relationship between reward-related brain function and peripheral inflammation

Inflammation is associated with both lower and higher activity in brain regions that process rewarding stimuli. How can both low and high sensitivity to rewards be associated with higher inflammation? We propose that one potential mechanism underlying these apparently conflicting findings pertains to how people pursue goals in their environment. This prediction is based on evidence that both an inability to disengage from unattainable goals and low interest in and pursuit of important life goals are associated with poor health outcomes, including inflammation. Accordingly, this study examined the relationship between reward-related brain function and peripheral inflammation among individuals with different levels of ambitious goal-striving tendencies. Eighty-three participants completed an ambitious goal-striving tendency measure, an fMRI Monetary Incentive Delay task assessing orbitofrontal cortex (OFC) and nucleus accumbens (NAc) activation during reward anticipation and outcome, and a venous blood draw to assess the inflammatory biomarkers interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and C-reactive protein, from which we computed an inflammation composite score. We observed a reward anticipation by goal-striving interaction on inflammation, such that high OFC and NAc activation to reward anticipation (but not outcome) were associated with more inflammation, among high goal-striving individuals. By contrast, low NAc activation during reward anticipation (but not outcome) was associated with more inflammation, among low goal-striving individuals. The current study provides further evidence that both blunted and elevated reward function can be associated with inflammation. It also highlights the role that goal-striving tendencies may play in moderating the relationship between neural reward anticipation and inflammation.     

Cognitive function and its relationship with brain structure in myotonic dystrophy type 1

Studies have shown relationships between white matter abnormalities and cognitive dysfunction in myotonic dystrophy type 1 (DM1), but comprehensive analysis of potential structure–function relationships are lacking. Fifty adult‐onset DM1 individuals (33 female) and 68 unaffected adults (45 female) completed the Wechsler Adult Intelligence Scale‐IV (WAIS‐IV) to determine the levels and patterns of intellectual functioning. Neuroimages were acquired with a 3T scanner and were processed with BrainsTools. Regional brain volumes (regions of interest, ROIs) were adjusted for inter‐scanner variation and intracranial volume. Linear regression models were conducted to assess if group by ROI interaction terms significantly predicted WAIS‐IV composite scores. Models were adjusted for age and sex. The DM1 group had lower Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores than the unaffected group (PRI t₍₁₁₃₎ = ?3.28, p = 0.0014; WMI t₍₁₁₄₎ = ?3.49, p = 0.0007; PSI t₍₁₁₄₎ = ?2.98, p = 0.0035). The group by hippocampus interaction term was significant for both PRI and PSI (PRI (t₍₁₁₁₎ = ?2.82, p = 0.0057; PSI (t₍₁₁₂₎ = ?2.87, p = 0.0049)). There was an inverse association between hippocampal volume and both PRI and PSI in the DM1 group (the higher the volume, the lower the intelligence quotient scores), but no such association was observed in the unaffected group. Enlarged hippocampal volume may underlie some aspects of cognitive dysfunction in adult‐onset DM1, suggesting that increased volume of the hippocampus may be pathological.     

The relationship between gross motor function impairment in cerebral palsy and sleeping issues of children and caregivers

AimTo investigate, among children and adolescents with cerebral palsy (CP), the relationship between impairment of the gross motor function and: (i) child sleep disorders; (ii) the need for nocturnal support; and (iii) the quality of sleep of their caregivers.MethodsFor children, we considered their scores on the gross motor function measure (GMFM-88) and on the sleep disturbance scale for children (SDSC), besides analyzing qualitative features about their sleep. For caregivers, we considered their scores in the Pittsburgh sleep quality index (PSQI).ResultsOur sample was comprised of 87 participants with mean age of 11.4 years old (±3.4). We observed correlations between GMFM-88 and disorders of initiating and maintaining sleep (DIMS) (r = −0.22; p = 0.039), sleep–wake transition disorders (SWTD) (r = 0.26; p = 0.017) and disorders of arousal (DA) (r = 0.23; p = 0.033). Children receiving nocturnal support presented lower scores in the GMFM-88 (p = 0.001) and higher scores in the SDSC (p = 0.029). For the caregivers, we found no correlation between GMFM-88 and PSQI. Nonetheless, their PSQI scores correlated with the SDSC scores (r = 0.24; p = 0.027).ConclusionImpairment of the gross motor function correlated with DIMS and the need for nocturnal support but might not have an impact on the caregivers’ sleep, which in turn correlated with child sleep disorders.     

影像学分型与急性脑梗死患者认知功能关系的研究

目的探讨影像学分型与急性脑梗死患者认知功能关系。方法对136例急性大脑梗死患者于发病后24～72h内行颅脑MRI检查确定梗死部位、测量病灶大小并作出影像学分型，于发病1周内，在患者床前采用简易精神状态检查法（mini—mentalstate examination，MMSE），检测患者的认知功能，并同步进行事件相关电位P300的检测，判断患者认知功能的情况，对比分析应用MRI进行的影像学分型与认知功能关系。结果额叶、颞叶脑梗死患者的MMSE和WAIS—RC评分明显低于顶枕叶和基底节区梗死患者，P300潜伏时明显长于顶枕叶和基底节区梗死的患者，但其P300波幅低于顶枕叶和基底节区梗死的惠者；中梗死和多发性梗死患者的MMSE和WAIS—RC评分明显低于顶枕叶和基底节区梗死患者，B300潜伏时明显长于顶枕叶和基底节区梗死的患者，但其P300波幅低于顶枕叶和基底节区梗死的患者。结论影像学分型与急性脑梗死患者认知功能有相关性。     

The relationship between olfactory dysfunction and executive function in children with traumatic brain injury

Introduction: Olfactory dysfunction (OD) has been suggested as a possible marker of executive function (EF) deficits after traumatic brain injury (TBI) in adults. Little is known about the relationship between EF and OD in pediatric TBI (pTBI). This study aimed to investigate EF, explore the relationship between OD and EF, and determine the utility of olfactory performance as a marker of later EF in pTBI. It was hypothesized that (i) children with TBI would perform more poorly on EF measures relative to normative expectation; (ii) children with OD would perform more poorly on tests of EF than those with normal olfaction after TBI; and (iii) acute olfactory function would predict later EF for children with TBI.

Method: This was a prospective longitudinal study. Twenty seven children aged 8–16 with TBI completed olfactory assessment using the University of Pennsylvania Smell Identification Test at 0–3, 8 and 18 months post injury. Assessment of EF occurred at 8 and 18 month follow-up.

Results: At 8 month follow-up the pTBI cohort did not demonstrate a consistent pattern of impairment in EF, contrary to our first hypothesis. Children with OD showed significantly poorer performance on a single EF measure of Fluency when compared to those with normal olfaction at 8 months post injury, partially supporting our second hypothesis. Acute olfactory function did not significantly predict EF outcomes at either 8 or 18 months post injury.

Conclusions: Overall our findings provide little support for a significant relationship between EF and OD in pTBI. In particular, there was no strong evidence that acute olfactory function is an accurate predictor of later EF in pTBI. Given the dearth of pediatric research, the limitations of our study and the potential significance of acute olfactory performance as an early marker of later EF deficits in children, further investigation is warranted.     

The relationship between volumetric brain changes and cognitive function: a family study on schizophrenia.

BACKGROUND: We examined the cerebral correlates of intelligence, memory, and executive processing in 56 patients with schizophrenia or schizoaffective disorder and 90 of their nonpsychotic relatives to establish whether the pattern of structure--function relationships in these two groups was different from that in 55 control subjects. METHODS: Magnetic resonance imaging data were acquired, and volumetric measurements were made for whole brain, prefrontal region, lateral ventricles, third ventricle, temporal lobes, hippocampi, and cerebellum. RESULTS: In the total sample, full intelligence quotient (IQ) and verbal IQ correlated with the volume of the whole brain and right hippocampus; the latter was also associated with performance IQ. Left hippocampal size was associated with verbal IQ and, in control subjects and nonpsychotic relatives only, with estimated full IQ. Delayed verbal memory was linked to cerebellar and inversely to left hippocampal volume. Discrepancies in the relationship pattern emerged in patients with schizophrenia between left hippocampus and measures of IQ and verbal memory. CONCLUSIONS: The latter data indicate a loss of a normal structure--function relationship in schizophrenia and might reflect a functional compensation occurring secondary to early neurodevelopmental impairment.     

Connectivity and complexity: the relationship between neuroanatomy and brain dynamics.

Nervous systems facing complex environments have to balance two seemingly opposing requirements. First, there is a need quickly and reliably to extract important features from sensory inputs. This is accomplished by functionally segregated (specialized) sets of neurons, e.g. those found in different cortical areas. Second, there is a need to generate coherent perceptual and cognitive states allowing an organism to respond to objects and events, which represent conjunctions of numerous individual features. This need is accomplished by functional integration of the activity of specialized neurons through their dynamic interactions. These interactions produce patterns of temporal correlations or functional connectivity involving distributed neuronal populations, both within and across cortical areas. Empirical and computational studies suggest that changes in functional connectivity may underlie specific perceptual and cognitive states and involve the integration of information across specialized areas of the brain. The interplay between functional segregation and integration can be quantitatively captured using concepts from statistical information theory, in particular by defining a measure of neural complexity. Complexity measures the extent to which a pattern of functional connectivity produced by units or areas within a neural system combines the dual requirements of functional segregation and integration. We find that specific neuroanatomical motifs are uniquely associated with high levels of complexity and that such motifs are embedded in the pattern of long-range cortico-cortical pathways linking segregated areas of the mammalian cerebral cortex. Our theoretical findings offer new insight into the intricate relationship between connectivity and complexity in the nervous system.     

The structure function relationship for the Prion protein

Central to Prion diseases is the normal endogenous Prion protein, PrPC. In spite of years of research the exact function of this protein remains enigmatic. Numerous binding partners have been identified for PrPC and due to the presence of a repeated sequence of PHGGGWGQ in the proteins amino-terminus it can bind metal ions. The protein is a complex molecule and each portion of PrPC possesses different roles for function and/ or trafficking. As understanding the role of PrPC is central to these disorders the structure/function relationship will be reviewed here.     

Psychoendocrine investigation in schizophrenia: relationship between pituitary-gonadal function and behavior

The Authors examine possible connections between the schizophrenic syndrome and the hypothalamo-pituitary-gonadal system, assuming that hormonal impairments may correlate with the appearance and development of peculiar behavioral features. The hormonal status and the behavioral parameters have been examined before, during and after a psychopharmacological therapy, and a combination of a psychopharmacological-hormonal treatment. Data have been obtained in 12 male hebephrenic schizophrenics, aged 18-36 years, with onset of the disease between 12 months and 20 years before our experiments. The patients were treated for 30 days with Haloperidol (6 mg.i.m.p.d. to a total dose of 180 mg.) and then for 45 days with Haloperidol at the same dose in combination with Chorionic Gonadotrophin (5000 I.U.i.m. twice a week for a total dose of 60.000 I.U.). The following hormonal assays were performed: total urinary gonadotrophins, serum FSH and LH, total urinary 17 ketosteroids, total urinary estrogens, serum testosterone. The hormonal assays were performed twice prior to therapy, twice during the Haloperidol therapy (12th and 26th days) twice during the Haloperidol plus HCG therapy (20th and 40th day) and 1 month after the withdrawal of the therapy. The psychological-behavioral parameters were examined through the Wittenborn Rating Scale. The result obtained seem to reveal a stimulatory effect of the Haloperidol plus HCG therapy on the deficient hormonal status. Moreover, it is evident that a constant correlation exists between biochemical improvement and behavioral improvement, especially in regard to affectivity disorders, adjustment to reality, active behavior.     

Three principles of brain function and structure.

A large part of the presently available data in the physiology and anatomy of the nervous system is found to be consistent with three comparatively simple principles. Phrased in the terminology introduced in the paper, the first of these expresses the assumption of specificity of neuron response, the second states the biological equivalent of a maximum principle believed to govern the formation and modication of interneuronal connectivity, and the third describes the probable role of genetically determined gross anatomy in securing the groundwork for developing neurospecificity. A number of remarks are included, and an extensive discussion of the evidence behind the principles.     

Endovascular deep brain stimulation: Investigating the relationship between vascular structures and deep brain stimulation targets

BackgroundEndovascular delivery of current using ‘stentrodes’ – electrode bearing stents – constitutes a potential alternative to conventional deep brain stimulation (DBS). The precise neuroanatomical relationships between DBS targets and the vascular system, however, are poorly characterized to date.ObjectiveTo establish the relationships between cerebrovascular system and DBS targets and investigate the feasibility of endovascular stimulation as an alternative to DBS.MethodsNeuroanatomical targets as employed during deep brain stimulation (anterior limb of the internal capsule, dentatorubrothalamic tract, fornix, globus pallidus pars interna, medial forebrain bundle, nucleus accumbens, pedunculopontine nucleus, subcallosal cingulate cortex, subthalamic nucleus, and ventral intermediate nucleus) were superimposed onto probabilistic vascular atlases obtained from 42 healthy individuals. Euclidian distances between targets and associated vessels were measured. To determine the electrical currents necessary to encapsulate the predefined neurosurgical targets and identify potentially side-effect inducing substrates, a preliminary volume of tissue activated (VTA) analysis was performed.ResultsSix out of ten DBS targets were deemed suitable for endovascular stimulation: medial forebrain bundle (vascular site: P1 segment of posterior cerebral artery), nucleus accumbens (vascular site: A1 segment of anterior cerebral artery), dentatorubrothalamic tract (vascular site: s2 segment of superior cerebellar artery), fornix (vascular site: internal cerebral vein), pedunculopontine nucleus (vascular site: lateral mesencephalic vein), and subcallosal cingulate cortex (vascular site: A2 segment of anterior cerebral artery). While VTAs effectively encapsulated mfb and NA at current thresholds of 3.5 V and 4.5 V respectively, incremental amplitude increases were required to effectively cover fornix, PPN and SCC target (mean voltage: 8.2 ± 4.8 V, range: 3.0–17.0 V). The side-effect profile associated with endovascular stimulation seems to be comparable to conventional lead implantation. Tailoring of targets towards vascular sites, however, may allow to reduce adverse effects, while maintaining the efficacy of neural entrainment within the target tissue.ConclusionsWhile several challenges remain at present, endovascular stimulation of select DBS targets seems feasible offering novel and exciting opportunities in the neuromodulation armamentarium.     

Dehydration affects brain structure and function in healthy adolescents

It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross‐over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto‐parietal blood‐oxygen‐level‐dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo‐spatial processing. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.