Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive-compulsive disorder

Jung WH, Kang D‐H, Han JY, Jang JH, Gu B‐M, Choi J‐S, Jung MH, Choi C‐H, Kwon JS. Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder. Objective: Obsessive–compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD. Method: Twenty unmedicated patients with OCD and 20 age‐, sex‐, and IQ‐matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task. Results: Compared with controls, patients with OCD showed increased ventral striatal activation in the no‐loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no‐gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation. Conclusion: These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.     

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.     

Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [¹¹C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine‐addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine‐addicted individuals. Synapse 64:397–402, 2010. © 2009 Wiley‐Liss, Inc.     

Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder

The basal ganglia represents a key component of the pathophysiological model for obsessive-compulsive disorder (OCD). This brain region is part of several neural circuits, including the orbitofronto-striatal circuit and dorsolateral prefronto-striatal circuit. There are, however, no published studies investigating those circuits at a network level in non-medicated patients with OCD. Resting state functional magnetic resonance imaging scans were obtained from 20 non-medicated patients with OCD and 23 matched healthy volunteers. Voxelwise statistical parametric maps testing strength of functional connectivity of three striatal seed regions of interest (ROIs) with remaining brain regions were calculated and compared between groups. We performed additional correlation analyses between strength of connectivity and the severity scores for obsessive-compulsive symptoms, depression, and anxiety in the OCD group. Positive functional connectivity with the ventral striatum was significantly increased (P_corrected <.05) in the orbitofrontal cortex, ventral medial prefrontal cortex and dorsal lateral prefrontal cortex of subjects with OCD. There was no significant correlation between measures of symptom severity and the strength of connectivity (P_uncorrected <.001). This is the first study to investigate the corticostriatal connectivity in non-medicated patients with OCD. These findings provide the first direct evidence supporting a pathophysiological model involving basal ganglia circuitry in OCD.     

有无遗传史的强迫症患者前额叶磁共振质子波谱对照研究

目的 探讨有无遗传史强迫症患者前额叶神经代谢物的变化.方法 采用磁共振质子波谱技术对有遗传史强迫症组(10例)、无遗传史强迫症组(14例)和对照组(12例)的内侧前额叶皮质N-乙酰天冬氨酸(NAA)、肌酸(Cr)和胆碱复合物(Cho)的代谢物含量进行对照研究.结果 有遗传史强迫症组的NAA值(46±8)和NAA/Cr值(1.59±0.24)分别高于对照组的NAA值(37±7)(方差分析LSD法校正,P=0.024)和NAA/Cr值(1.31±0. 21)(方差分析LSD法校正,P=0.006);有遗传史强迫症组的NAA值也高于无遗传史强迫症组的NAA值(37±10)(方差分析LSD法校正,P=0.021);无遗传史强迫症组与对照组相比,NAA/Cr值可见增加趋势(方差分析LSD法校正,P=0.066).结论 有遗传史强迫症患者的神经代谢物NAA与对照组和无遗传史强迫症患者相比在内侧前额叶皮质明显升高.     

Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression

BACKGROUND: Serotonin reuptake inhibitors (SRIs) effectively treat both major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). We compared and contrasted the functional neuroanatomical effects of SRIs in OCD and MDD as these 2 disorders occurred separately and concurrently by measuring pretreatment to posttreatment cerebral glucose metabolic changes in OCD vs MDD vs concurrent OCD + MDD. METHODS: We obtained [(18)F]fluorodeoxyglucose positron emission tomography (PET) brain scans on 25 subjects with OCD, 25 with MDD, and 16 with concurrent OCD + MDD before and after 8 to 12 weeks of treatment with paroxetine hydrochloride. Controls (n = 16) were scanned 10 to 12 weeks apart without treatment. Treatment response was defined as a more than 25% decline in OCD symptom severity, a more than 50% decline in MDD severity, and "much improved" clinical global impression. RESULTS: Although all patient groups received the same paroxetine dose for the same duration, regional metabolic changes differed significantly among diagnostic groups. Subjects with OCD alone showed significant metabolic decreases in the right caudate nucleus, right ventrolateral prefrontal cortex (VLPFC), bilateral orbitofrontal cortex, and thalamus that were not seen in any other group. Both the MDD and concurrent OCD + MDD groups showed metabolic decreases in the left VLPFC and increases in the right striatum. Treatment response was associated with a decrease in striatal metabolism in nondepressed OCD patients but with an increase in striatal activity in patients with OCD + MDD. CONCLUSIONS: Brain metabolic responses to SRIs are both disorder-specific and response-specific. They vary according to the underlying pathophysiology of the patient and the degree of symptomatic improvement.     

Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression.

BACKGROUND: Bipolar disorder (BD) is characterised by abnormalities in mood and emotional processing, but the neural correlates of these, their relationship to depressive symptoms, and the similarities with deficits in major depressive disorder (MDD) remain unclear. We compared responses within subcortical and prefrontal cortical regions to emotionally salient material in patients with BP and MDD using functional magnetic resonance imaging. METHODS: We measured neural responses to mild and intense expressions of fear, happiness, and sadness in euthymic and depressed BD patients, healthy control subjects, and depressed MDD patients. RESULTS: Bipolar disorder patients demonstrated increased subcortical (ventral striatal, thalamic, hippocampal) and ventral prefrontal cortical responses particularly to mild and intense fear, mild happy, and mild sad expressions. Healthy control subjects demonstrated increased subcortical responses to intense happy and mild fear, and increased dorsal prefrontal cortical responses to intense sad expressions. Overall, MDD patients showed diminished neural responses to all emotional expressions except mild sadness. Depression severity correlated positively with hippocampal response to mild sadness in both patient groups. CONCLUSIONS: Compared with healthy controls and MDD patients, BD patients demonstrated increased subcortical and ventral prefrontal cortical responses to both positive and negative emotional expressions.     

Altered Striatal Functional Connectivity in Subjects With an At-Risk Mental State for Psychosis

Recent functional imaging work in individuals experiencing an at-risk mental state (ARMS) for psychosis has implicated dorsal striatal abnormalities in the emergence of psychotic symptoms, contrasting with earlier findings implicating the ventral striatum. Our aims here were to characterize putative dorsal and ventral striatal circuit-level abnormalities in ARMS individuals using resting-state functional magnetic resonance imaging (fMRI) and to investigate their relationship to positive psychotic symptoms. Resting-state fMRI was acquired in 74 ARMS subjects and 35 matched healthy controls. An established method for mapping ventral and dorsal striatal functional connectivity was used to examine corticostriatal functional integrity. Positive psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental State and the Positive and Negative Syndrome Scale. Compared with healthy controls, ARMS subjects showed reductions in functional connectivity between the dorsal caudate and right dorsolateral prefrontal cortex, left rostral medial prefrontal cortex, and thalamus, and between the dorsal putamen and left thalamic and lenticular nuclei. ARMS subjects also showed increased functional connectivity between the ventral putamen and the insula, frontal operculum, and superior temporal gyrus bilaterally. No differences in ventral striatal (ie, nucleus accumbens) functional connectivity were found. Altered functional connectivity in corticostriatal circuits were significantly correlated with positive psychotic symptoms. Together, these results suggest that risk for psychosis is mediated by a complex interplay of alterations in both dorsal and ventral corticostriatal systems.Key words: ARMS, fMRI, resting state, striatum     

Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder.

BACKGROUND: Although abnormalities in reward processing have been proposed to underlie attention-deficit/hyperactivity disorder (ADHD), this link has not been tested explicitly with neural probes. METHODS: This hypothesis was tested by using fMRI to compare neural activity within the striatum in individuals with ADHD and healthy controls during a reward-anticipation task that has been shown previously to produce reliable increases in ventral striatum activity in healthy adults and healthy adolescents. Eleven adolescents with ADHD (5 off medication and 6 medication-na?ve) and 11 healthy controls (ages 12-17 y) were included. Groups were matched for age, gender, and intelligence quotient. RESULTS: We found reduced ventral striatal activation in adolescents with ADHD during reward anticipation, relative to healthy controls. Moreover, ventral striatal activation was negatively correlated with parent-rated hyperactive/impulsive symptoms across the entire sample. CONCLUSIONS: These findings provide neural evidence that symptoms of ADHD, and impulsivity or hyperactivity in particular, may involve diminished reward anticipation, in addition to commonly observed executive dysfunction.     

Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat.

The anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to examine the topographical organization of the projections to the striatum arising from the various cytoarchitectonic subdivisions of the prefrontal cortex in the rat. The relationship of the prefrontal cortical fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin-immunohistochemistry. The prefrontal cortex projects bilaterally with an ipsilateral predominance to the striatum, sparing only the lateral part of the caudate-putamen complex. Each of the cytoarchitectonic subfields of the prefrontal cortex has a longitudinally oriented striatal terminal field that overlaps slightly with those of adjacent prefrontal areas. The projections of the medial subdivision of the prefrontal cortex distribute to rostral and medial parts of the striatum, whereas the lateral prefrontal subdivision projects to more caudal and lateral striatal areas. The terminal fields of the orbital prefrontal areas involve midventral and ventromedial parts of the caudate-putamen complex. The projection of the ventral orbital area overlaps with that of the prelimbic area in the ventromedial part of the caudate-putamen. In the "shell" region of the nucleus accumbens, fibres arising from the prelimbic area concentrate in areas of high cell density that are weakly enkephalin-immunoreactive, whereas fibres from the infralimbic area avoid such areas. Rostrolaterally in the "core" region of the nucleus accumbens, fibres from deep layer V and layer VI of the dorsal part of the prelimbic area avoid the enkephalin-positive areas surrounding the anterior commissure and distribute in an inhomogeneous way over the intervening moderately enkephalin-immunoreactive compartment. The other prefrontal afferents show only a preference for, but are not restricted to, the latter compartment. In the border region between the nucleus accumbens and the ventromedial part of the caudate-putamen complex, patches of strong enkephalin immunoreactivity receive prefrontal cortical input from deep layer V and layer VI, whereas fibres from more superficial cortical layers project to the surrounding matrix. Individual cytoarchitectonic subfields of the prefrontal cortex thus have circumscribed terminal domains in the striatum. In combination with data on the organization of the midline and intralaminar thalamostriatal and thalamoprefrontal projections, the present results establish that the projections of the prefrontal cortical subfields converge in the striatum with those of their midline and intralaminar afferent nuclei. The present findings further demonstrate that the relationship of the prefrontal corticostriatal fibres with the neurochemical compartments of the ventral striatum can be influenced by both the areal and the laminar origin of the cortical afferents, depending on the particular ventral striatal region under consideration.     

fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder

BACKGROUND: Previous studies suggest that a neural circuit involving over-activation of cortical, paralimbic, limbic, and striatal structures may underlie OCD symptomatology, but results may have been limited by medication use in those studies. To address this, we examined the effects of symptom induction on fMRI neural activation in medication-free patients with OCD. METHODS: Seven outpatients with OCD were exposed to individually tailored provocative and innocuous stimuli during fMRI scans. Self-ratings of OCD symptoms were performed prior to each scan and after exposure to stimuli. Images were analyzed as composite data sets and individually. RESULTS: Stimulus presentation was associated with significant increases in OCD self-ratings. Significant activation was demonstrated in several regions of the frontal cortex (orbitofrontal, superior frontal, and the dorsolateral prefrontal); the anterior, medial and lateral temporal cortex; and the right anterior cingulate. Right superior frontal activation inversely correlated with baseline compulsion symptomatology and left orbitofrontal cortical activation was inversely associated with changes in OCD self-ratings following provocative stimuli. CONCLUSIONS: These results in unmedicated patients are consistent with those from previous studies with medicated patients and suggest that OCD symptomatology is mediated by multiple brain regions including the anterior cingulate as well as frontal and temporal brain regions.     

Disorder-specific dysfunctions in patients with attention-deficit/hyperactivity disorder compared to patients with obsessive-compulsive disorder during interference inhibition and attention allocation

Background: Abnormalities in inhibitory control and underlying fronto‐striatal networks is common to both attention deficit hyperactivity disorder (ADHD) and obsessive‐compulsive‐disorder (OCD). The aim of this study was to investigate disorder‐specific abnormalities in neural networks mediating interference inhibition and selective attention. Method: Event‐related functional magnetic resonance imaging (fMRI) was used to compare brain activation of boys with ADHD (18), with OCD (10), and healthy boys during (20) during a Simon task that measures interference inhibition and controls for and therefore comeasures attention allocation. Results: During interference inhibition, both patient groups shared mesial frontal dysfunction compared to controls. Disorder‐specific dysfunctions were observed in OCD patients in dorsolateral prefrontal cortex during the oddball condition and in ADHD patients in inferior parietal lobe during interference inhibition and in caudate and posterior cingulate during the simpler oddball condition. The decreased activation in caudate and cingulate in ADHD was furthermore negatively correlated with ADHD symptoms and positively with OCD behavioral traits. Conclusions: The study shows that ADHD and OCD patients have shared but also disorder‐specific brain dysfunctions during interference inhibition and attention allocation. Both disorders shared dysfunction in mesial frontal cortex. Disorder‐specific dysfunctions, however, were observed in dorsolateral prefrontal cortex in OCD patients and in caudate, cingulate, and parietal brain regions in ADHD patients. The disorder‐specific dissociation of striato‐cingulate activation that was increased in OCD compared to ADHD patients, was furthermore inversely related to the symptomatology of the two disorders, and may potentially reflect differential dopamine modulation of striatal brain regions. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Paediatric obsessive–compulsive disorder,a neurodevelopmental disorder?: Evidence from neuroimaging

ObjectiveTo present an overview of neuroimaging data on paediatric obsessive–compulsive disorder (OCD) and discuss implications for further research.MethodMedline PsycINFO databases and reference lists were searched for relevant articles. All neuroimaging studies up to October 1, 2008 involving children and adolescents with obsessive–compulsive disorder were included.ResultsTwenty-eight neuroimaging studies using various neuroimaging techniques (CT (2) MRI (15) MRS (8) and SPECT (2) fMRI (2) but no PET or DTI) including a total of 462 paediatric patients were identified. A number of findings indicate a dysfunction of the prefrontal–striatal–thalamic circuit with the involvement of other basal ganglia structures (putamen globus pallidus) and the thalamus in contrast to adult studies which report mainly involvement of the caudate nucleus and orbitofrontal cortex. Several findings point at an aberrant development of the brain in paediatric OCD, patients when compared with healthy controls.ConclusionNeuroimaging studies have contributed to our understanding of the neurobiological basis of paediatric OCD. This review provides an agenda for further theory driven research in particular aimed at identifying a critical window of abnormal maturation of prefrontal–striatal–thalamic and limbic circuitry in paediatric OCD patients.     

Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers.

BACKGROUND: The neural correlates of anxiety associated with obsessive-compulsive symptomlike provocation in normal volunteers are unknown. METHODS: Ten healthy volunteers participated in four functional magnetic resonance experiments. Subjects were scanned while viewing alternating blocks of emotional (normally aversive, washing-relevant, checking-relevant, or hoarding-relevant pictures) and neutral pictures, and imagining scenarios related to the content of each picture type. Nonparametric brain mapping analyses were used. RESULTS: In response to the provocative pictures in all experiments, increases in subjective anxiety and activation in bilateral ventral prefrontal, limbic, dorsal prefrontal, and visual regions were demonstrated. Anxiety related to different symptom dimensions was associated with different patterns of activation: provocation of washing-relevant anxiety predominantly activated dorsal and ventral prefrontal regions; checking-relevant anxiety predominantly activated dorsal prefrontal regions; and hoarding-relevant anxiety predominantly activated ventral prefrontal regions and the left amygdala. CONCLUSIONS: Our findings support a dimensional model of obsessive-compulsive disorder (OCD) whereby 1) the brain systems implicated in the mediation of anxiety in response to symptom-related material in normal subjects are similar to those identified in OCD patients during symptom provocation, and 2) anxiety associated with different symptom dimensions is associated with differential patterns of activation of these neural systems. Further investigation of the neural basis of OCD symptom dimensions is required.     

Reduced fronto-callosal fiber integrity in unmedicated OCD patients: a diffusion tractography study

It is widely accepted that abnormalities in the frontal area of the brain underpin the pathophysiology of obsessive‐compulsive disorder (OCD). Fundamental to this investigation is the delineation of frontal white matter tracts including dorsal and ventral frontal projections of interhemispheric connections. While previous investigations of OCD have examined the dorsal and ventral frontal regions, the corresponding callosal connections have not been investigated, despite their importance. We recruited twenty patients with OCD (15 drug‐naïve and 5 currently unmedicated) and demographically similar healthy controls, and conducted fiber tractography and post hoc quantitative analysis using diffusion tensor imaging. We extracted fractional anisotropy (FA) of the fronto‐callosal fibers along the entire length of the tract. Function‐specific [by the Brodmann area region‐of‐interest (ROI) approach] and region‐specific (by the length‐parameterization approach) tracts were defined. In addition, we devised a new index of dorsal‐ventral imbalance (DVII) of fiber integrity. Significant FA decreases were observed in orbitofrontal and dorsolateral prefrontal projections of the corpus callosum (P < 0.05, false discovery rate‐corrected) with higher function/region sensitivity than voxel‐based or ROI‐based approaches. Importantly, OCD patients also exhibited significantly higher ventral‐greater‐than‐dorsal asymmetry of FA values than normal controls (P < 0.05, FDR‐corrected). This study is the first to investigate fiber integrity in the dorsal/ventral frontal parts of the callosal tractography in unmedicated OCD patients. Using a more quantitative method in terms of functional and regional specificity than previous studies, we report abnormalities in interhemispheric connectivity of both dorsal and ventral networks in the pathophysiology of OCD. Hum Brain Mapp 33:2441–2452, 2012. © 2011 Wiley Periodicals, Inc.     

Disorder‐specific dysfunction in right inferior prefrontal cortex during two inhibition tasks in boys with attention‐deficit hyperactivity disorder compared to boys with obsessive–compulsive disorder

Background:

Inhibitory dysfunction is a key behavioral and cognitive phenotype of attention‐deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD). Both disorders show neuropsychological deficits and fronto‐striatal dysfunction during tasks of motor response inhibition and cognitive flexibility. This study investigates differences and commonalities in functional neural networks mediating inhibitory control between adolescents with ADHD and those with OCD to identify disorder‐specific neurofunctional markers that distinguish these two inhibitory disorders.

Methods:

Event‐related fMRI was used to compare brain activation between 20 healthy boys, 18 (Stop task) or 12 boys (Switch task) with ADHD, and 10 boys with OCD during a tracking Stop task that measures inhibition and stopping failure and during a visual–spatial switching task measuring cognitive flexibility.

Results:

Both patient groups shared brain dysfunction compared to healthy controls in right orbitofrontal (successful inhibition) and left dorsolateral prefrontal cortices (failed inhibition). Right inferior prefrontal dysfunction, however, was disorder‐specific to ADHD during both tasks. Left inferior prefrontal dysfunction during the Switch task was significant in children with ADHD relative to controls, but only reached a trend in patients with OCD. Patients with ADHD furthermore showed disorder‐specific dysfunction in left basal ganglia and cingulate gyrus during the Switch task.

Conclusions:

Patients with ADHD compared to those with OCD have both common and distinct dysfunctions during inhibitory control. The most consistently reported functional abnormality in children with ADHD in right inferior prefrontal cortex during inhibitory control appears to be disorder‐specific when compared to patients with OCD and may be a specific neurofunctional biomarker of ADHD. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.

     

Anatomic organization of basoventral and mediodorsal visual recipient prefrontal regions in the rhesus monkey

The sources of ipsilateral cortical afferent projections to basoventral and mediodorsal prefrontal cortices that receive some visual input were studied with retrograde tracers (horseradish peroxidase or fluorescent dyes) in eight rhesus monkeys. The basoventral regions injected with tracers included basal (orbital) areas 11 and 12, lateral area 12, and ventral area 46. The mediodorsal regions included portions of medial area 32 and the caudal part of dorsal area 8. These sites represent areas within basoventral and mediodorsal prefrontal cortices that show a gradual increase in architectonic differentiation in a direction from the least differentiated orbital and medial limbic cortices toward the most differentiated cortices in the arcuate concavity. The results showed that the visual input to basoventral and mediodorsal prefrontal cortices originated largely in topographically distinct visual areas. Thus, basoventral sites received most of their visual cortical projections from the inferior temporal cortex. The rostral inferior temporal region was the predominant source of visual projections to orbital prefrontal sites, whereas lateral area 12 and ventral area 46 also received projections which were found more caudally. In contrast, mediodorsal prefrontal sites received most of their visual projections from dorsolateral and dorsomedial visual areas. The cells of origin were located in rostromedial visual cortices after injection of retrograde tracers in area 32 and in more caudal medial and dorsolateral visual areas after injection in caudal area 8. The latter also received substantial projections from visuomotor regions in the caudal portion of the lateral bank of the intraparietal sulcus. These results suggest that the basoventral prefrontal cortices are connected with ventral visual areas implicated in pattern recognition and discrimination, whereas the mediodorsal cortices are connected with medial and dorsolateral occipital and parietal areas associated with visuospatial functions. In addition, the prefrontal areas studied received projections from auditory and/or somatosensory cortices, from areas associated with more than one modality, and from limbic regions. Orbital area 12 seemed to be a major target of projections from somatosensory cortices and the rostral portion of medial area 32 received substantial projections from auditory cortices. The least architectonically differentiated areas (orbital area 11 and medial area 32) had more widespread corticocortical connections, including strong links with limbic cortices.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates

The prefrontal cortex has been implicated in a variety of cognitive and executive processes, including working memory, decision-making, inhibitory response control, attentional set-shifting and the temporal integration of voluntary behaviour. This article reviews current progress in our understanding of the rodent prefrontal cortex, especially evidence for functional divergence of the anatomically distinct sub-regions of the rat prefrontal cortex. Recent findings suggest clear distinctions between the dorsal (precentral and anterior cingulate) and ventral (prelimbic, infralimbic and medial orbital) sub-divisions of the medial prefrontal cortex, and between the orbitofrontal cortex (ventral orbital, ventrolateral orbital, dorsal and ventral agranular cortices) and the adjacent medial wall of the prefrontal cortex. The dorso-medial prefrontal cortex is implicated in memory for motor responses, including response selection, and the temporal processing of information. Ventral regions of the medial prefrontal cortex are implicated in interrelated 'supervisory' attentional functions, including attention to stimulus features and task contingencies (or action-outcome rules), attentional set-shifting, and behavioural flexibility. The orbitofrontal cortex is implicated in lower-order discriminations, including reversal of stimulus-reward associations (reversal learning), and choice involving delayed reinforcement. It is anticipated that a greater understanding of the prefrontal cortex will come from using tasks that load specific cognitive and executive processes, in parallel with discovering new ways of manipulating the different sub-regions and neuromodulatory systems of the prefrontal cortex.     

Heightened central affective response to visceral sensations of pain and discomfort in IBS

Background Typically, conventional functional imaging methods involve repeated exposures to sensory stimulation. In rectal distension (RD) studies that involve multiple distensions, however, it is difficult to disambiguate the central response to RD from pathological alterations in peripheral neural responses associated with relaxation and accommodation of the rectum. Methods This study addressed potential confounders found in previous imaging studies by collecting functional magnetic resonance imaging studies (fMRI) data during a single slow ramp‐tonic distension paradigm and analysing fMRI signal changes using independent component analysis. Key Results Compared with controls, IBS participants showed increased activation of the anterior cingulate cortices, insula and ventral medial prefrontal regions suggesting heightened affective responses to painful visceral stimuli. In addition, the failure by IBS patients to down‐regulate activity within ventral medial prefrontal and the posterior cingulate/precuneus regions was suggestive of reduced sensitivity to somatic changes and delayed shifts away from rest in `default network' activity patterns. Controls showed heightened activation of the thalamus, striatal regions and dorsolateral prefrontal cortex suggesting greater arousal and salience‐driven sustained attention reactions and greater modulation of affective responses to discomfort and pain. Conclusion&Inferences This work points to alterations in the central response to visceral pain and discomfort in IBS, highlighting diminished modulation and heightened internalization of affective reactions.     

强迫症与抑郁症的脑单光子发射计算机断层扫描对照研究

目的探讨强迫症、抑郁症局部脑血流量(rCBF)特点。方法应用单光子发射计算机断层扫描(SPECT)技术,对首发且未经治疗的39例强迫症患者、36例抑郁症患者和39名正常人于静息状态下行脑血流显像。以小脑皮质的放射性计数值为参考,对局部脑血流进行半定量分析。结果强迫症组两侧前额叶、前颞叶rCBF高于正常组(P<0.01);抑郁症组两侧前额叶、枕叶、扣带回及右前颞叶、右顶叶rCBF低于正常组(P<0.05);在两侧前额叶、前颞叶、顶叶、枕叶及右后额叶、扣带回,强迫症组rCBF高于抑郁症组(P<0.05)。结论强迫症组的前额叶及前颞叶呈高灌注改变,抑郁症组脑血流普遍低灌注,SPECT技术可望作为二者鉴别诊断的客观依据之一。