The Caudate Nucleus: Its Connections, Surgical Implications, and Related Complications.

BACKGROUND: The caudate nucleus is a C-shaped structure that is located in the center of the brain and is divided into 3 parts: the head, body, and tail. METHODS: We detail the anatomic connections, relationships with other basal ganglia structures, and clinical implications of injury to the caudate nucleus. RESULTS: Anatomically, the most inferior transcapsular gray matter is the lentiform peduncle, which is the connection between the lentiform nucleus and caudate nucleus as well as the amygdala. The border between the tail and body of the caudate nucleus is the posterior insular point. The tail of the caudate nucleus is extraependymal in some parts and intraependymal in some parts of the roof of the temporal horn of the lateral ventricle. The tail of the caudate nucleus crosses the inferior limiting sulcus (temporal stem), and section of the tail during approaches to lesions involving the temporal stem may cause motor apraxia. The mean distance from the temporal limen point, which is the junction of the limen insula and inferior limiting sulcus, to the tail of the caudate nucleus in the temporal stem is 15.87 ± 3.10 mm. CONCLUSIONS: Understanding of the functional anatomy and connections of the distinct parts of the caudate nucleus is essential for deciding the extent of resection of lesions involving the caudate nucleus and the types of deficits that may be found postoperatively.

Bilateral Caudate Nucleus Infarctions Following Upper Gastrointestinal Bleeding.

A 75-year-old woman presented with consciousness disturbance accompanied by hematemesis. Brain imaging revealed ischemia in the bilateral caudate nuclei and right cerebral watershed area due to stenosis of the right anterior cerebral artery (ACA) and bilateral internal carotid arteries (ICA), and hypoperfusion in the right caudate nucleus. The patient's only symptom was abulia, which gradually resolved. Further brain scans showed that the ICA stenosis had improved, although the right ACA stenosis persisted. This was a rare case of bilateral caudate nucleus infarctions with a hemodynamic etiology.

Thalamic Diaschisis in Acute Ischemic Stroke: Occurrence, Perfusion Characteristics, and Impact on Outcome.

BACKGROUND AND PURPOSE: Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus. METHODS: One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations. RESULTS: ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD- patients (each with P<0.001). In the ITD+ group, larger cerebral blood flow (P=0.002) and cerebral blood volume (P<0.001) deficit volumes, as well as smaller cerebral blood flow-cerebral blood volume mismatch (P=0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with P>0.05). ITD had no influence on the development of subacute stroke complications. CONCLUSIONS: ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion-based trials.

Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease.

BACKGROUND AND PURPOSE: To assess the effect of unilateral large vessel disease upon the cerebral hemodynamic autoregulatory status in the basal ganglia of patients with steno-occlusive internal carotid artery (ICA) disease. MATERIALS AND METHODS: Twenty-five healthy volunteers and 38 patients with a unilateral symptomatic steno-occlusive ICA lesion and were investigated; 20 with a stenosis >50% and 18 with an occlusion. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were assessed with pseudo-continuous arterial spin labeling (ASL) magnetic resonance (MR) imaging before and after administration of acetazolamide. RESULTS: When compared to controls, the CVR in patients with ICA stenosis was significantly lower in the middle cerebral artery (MCA) territory (P<0.05), and in the caudate (P<0.05) and lentiform nucleus (P<0.05) of the hemisphere ipsilateral to the stenosis. The CVR in the caudate nucleus contralateral to the stenosis was significantly lower (P<0.05) as well. In patients with ICA occlusion, the CVR in the hemisphere ipsilateral to the occlusion as well as in the contralateral hemisphere was significantly lower in the MCA territory (P<0.05), the caudate (P<0.05) and lentiform nucleus (P<0.05), and in the thalamus (P<0.05). CONCLUSION: Perfusion ASL MR imaging shows impaired cerebral hemodynamic autoregulation of the basal ganglia in patients with steno-occlusive ICA disease both in the hemisphere ipsilateral as well as in the hemisphere contralateral to the stenosis or occlusion.

Causal connectivity alterations of cortical-subcortical circuit anchored on reduced hemodynamic response brain regions in first-episode drug-naïve major depressive disorder.

Some efforts were done to investigate the disruption of brain causal connectivity networks involved in major depressive disorder (MDD) using Granger causality (GC) analysis. However, the homogenous hemodynamic response function (HRF) assumption over the brain may disturb the inference of temporal precedence. Here we applied a blind deconvolution approach to examine the altered HRF shape in first-episode, drug-naïve MDD patients. The regions with abnormal HRF shape in patients were chosen as seeds to detect the GC alterations in MDD. The results demonstrated significantly decreased magnitude of spontaneous hemodynamic response of the orbital frontal cortex (OFC) and the caudate nucleus (CAU) in MDD comparing to healthy controls, suggesting MDD patients likely had alterations in neurovascular coupling and cerebrovascular physiology in these two regions. GC mapping showed increased/decreased GC in OFC-/CAU centered networks in MDD. The outgoing GC values from OFC to anterior cingulate cortex and occipital regions were positively correlated with Hamilton Depression Scale (HAMD) scores, while the incoming GC from insula, middle and superior temporal gyrus to CAU were negatively correlated with HAMD scores of MDD. The abnormalities of directional connections in the cortico-subcortico-cerebellar network may lead to unbalanced integrating the emotional-related information for MDD, and further exacerbating depressive symptoms.

Correlation Between the Reduction in Lenticulostriate Arteries Caused by Hypertension and Changes in Brain Metabolism Detected With MRI.

OBJECTIVE: Hypertension can alter the vascular structure, mechanics, and function of small arteries and arterioles. It remains unknown whether microvascular changes are associated with brain metabolism. The purpose of this study was to analyze the correlation between the reduction in small arteries and changes in brain metabolism in patients with hypertension. SUBJECTS AND METHODS: The study population comprised 50 patients with hypertension and 50 volunteers without hypertension. The two groups underwent 3-T 3D time-of-flight MR angiography, and the numbers of lenticulostriate arteries (LSAs) were determined for both groups. Single-voxel proton MR spectroscopic data on the basal ganglia regions were also acquired. The ratios of N-acetylaspartate to creatine (NAA/Cr), myo-inositol to creatine (Mi/Cr), and choline to creatine (Cho/Cr) were measured. Statistical analysis was performed to evaluate the differences between the two groups with respect to metabolite ratios. RESULTS: The average total number of LSA stems on both sides in patients with hypertension was 5.12 ± 0.98 compared with 6.10 ± 0.95 in volunteers without hypertension (p < 0.0001). The NAA/Cr ratio decreased according to a reduction in the number of LSAs in the hypertension group, which was significantly reduced when the number of LSAs was 3 or fewer. CONCLUSION: Hypertension can lead to a statistically significant reduction in NAA/Cr ratio in the basal ganglia regions when the number of LSAs decreases to a certain extent. Reduced numbers of LSAs correlated with brain metabolism changes caused by hypertension, which can provide important insights for understanding the pathophysiologic mechanism of hypertension and may be valuable in evaluating this disease.

Clinical significance of blood supply to the internal capsule and basal ganglia.

Although the general vascular supply of the basal ganglia and internal capsule is well known, precise data are lacking regarding the variations of the vascular territories in the two regions. Twelve hemispheres were studied following an injection of coloured ink into the main cerebral arteries, namely the anterior cerebral (ACA), middle cerebral (MCA), anterior choroidal (AChA) and posterior cerebral artery (PCA). Serial sections of the injected hemispheres were taken in the axial or coronal plane. In 75% of the hemispheres, ACA perforators were seen to supply the inferomedial part of the head of the caudate nucleus and the anterior limb of the internal capsule, as well as the anterior and inferior portions of the putamen and globus pallidus. The MCA vessels perfused the superolateral part of the head and body of the caudate nucleus, the superior part of the entire internal capsule, most of the putamen and part of the globus pallidus. The AChA perforators perfused the medial segment of the globus pallidus, the inferior part of the posterior limb, the retrolenticular and sublenticular portions of the internal capsule, and occasionally its genu. The same segment of the globus pallidus and the inferior part of the genu of the internal capsule were most likely supplied by the perforators of the internal carotid artery. A predominance of ACA territory was noticed in one specimen (8.33%) and a predominance of MCA territory in two specimens (16.67%). The obtained anatomical data may help radiologic determination of perforators involved in ischemic events, as well as a better understanding of the neurological deficits in the same events.

String Vessel Formation is Increased in the Brain of Parkinson Disease.

BACKGROUND: String vessels are collapsed basement membrane without endothelium and have no function in circulation. String vessel formation contributes to vascular degeneration in Alzheimer disease. By comparing to age-matched control cases we have recently reported endothelial degeneration in brain capillaries of human Parkinson disease (PD). OBJECTIVE: Current study evaluated changes of basement membrane of capillaries, string vessel formation and their association with astrocytes, blood-brain-barrier integrity and neuronal degeneration in PD. METHODS: Brain tissue from human cases of PD and age-matched controls was used. Immunohistochemical staining for collagen IV, GFAP, NeuN, tyrosine hydroxylase, fibrinogen and Factor VIII was evaluated by image analysis in the substantia nigra, caudate nucleus and middle frontal gyrus. RESULTS: While the basement-membrane-associated vessel density was similar between the two groups, the density of string vessels was significantly increased in the PD cases, particularly in the substantia nigra. Neuronal degeneration was found in all brain regions. Astrocytes and fibrinogen were increased in the caudate nuclei of PD cases compared with control cases. CONCLUSIONS: Endothelial degeneration and preservation of basement membrane result in an increase of string vessel formation in PD. The data may suggest a possible role for cerebral hypoperfusion in the neuronal degeneration characteristic of PD, which needs further investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be associated with disruption of the blood-brain barrier in this brain region.

Noninvasive, neuron-specific gene therapy can be facilitated by focused ultrasound and recombinant adeno-associated virus.

Recombinant adeno-associated virus (rAAV) has shown great promise as a potential cure for neurodegenerative diseases. The existence of the blood-brain barrier (BBB), however, hinders efficient delivery of the viral vectors. Direct infusion through craniotomy is the most commonly used approach to achieve rAAV delivery, which carries increased risks of infection and other complications. Here, we report a focused ultrasound (FUS)-facilitated noninvasive rAAV delivery paradigm that is capable of producing targeted and neuron-specific transductions. Oscillating ultrasound contrast agents (microbubbles), driven by FUS waves, temporarily 'unlock' the BBB, allowing the systemically administrated rAAVs to enter the brain parenchyma, while maintaining their bioactivity and selectivity. Taking the advantage of the neuron-specific promoter synapsin, rAAV gene expression was triggered almost exclusively (95%) in neurons of the targeted caudate-putamen region. Both behavioral assessment and histological examination revealed no significant long-term adverse effects (in the brain and several other critical organs) for this combined treatment paradigm. Results from this study demonstrated the feasibility and safety for the noninvasive, targeted rAAV delivery, which might have open a new avenue in gene therapy in both preclinical and clinical settings.

Dissociated effects of anticipating smoking versus monetary reward in the caudate as a function of smoking abstinence.

BACKGROUND: Theories of addiction suggest that chronic smoking may be associated with both hypersensitivity to smoking and related cues and hyposensitivity to alternative reinforcers. However, neural responses to smoking and nonsmoking rewards are rarely evaluated within the same paradigm, leaving the extent to which both processes operate simultaneously uncertain. Behavioral evidence and theoretical models suggest that dysregulated reward processing may be more pronounced during deprivation from nicotine, but neuroimaging evidence on the effects of deprivation on reward processing is limited. The current study examined the impact of deprivation from smoking on neural processing of both smoking and monetary rewards. METHODS: Two separate functional magnetic resonance imaging scans were performed in 38 daily smokers, one after smoking without restriction and one following 24 hours of abstinence. A rewarded guessing task was conducted during each scan to evaluate striatal blood oxygen level-dependent response during anticipation of both smoking and monetary rewards. RESULTS: A significant reward type by abstinence interaction was observed in the bilateral caudate and medial prefrontal cortex during reward anticipation. The blood oxygen level-dependent response to anticipation of smoking reward was significantly higher and anticipation of monetary rewards was significantly lower during abstinence compared with nonabstinence. Attenuation of monetary reward-related activation during abstinence was significantly correlated with abstinence-induced increases in craving and withdrawal. CONCLUSIONS: These results provide the first direct evidence of dissociated effects of smoking versus monetary rewards as a function of abstinence. The findings suggest an important neural pathway that may underlie the choice to smoke in lieu of alternative reinforcement during a quit attempt.

Unusual case of bilateral caudate infarcts following pituitary apoplexy.

IMPORTANCE: Cerebral ischemia due to pituitary apoplexy is very rare. It may be caused by vasospasm or direct compression of cerebral vessels by the expanding mass. Bilateral caudate infarcts also are very rare. To our knowledge, this is the first case report that presents pituitary apoplexy causing compression of bilateral anterior cerebral artery branches and leading to bilateral caudate infarcts. OBSERVATIONS: An 81-year-old woman with a pituitary macroadenoma presented with circulatory shock due to pituitary apoplexy. Neurological examination revealed new asymmetric quadriparesis with chronic bilateral visual disturbance. On brain magnetic resonance imaging, she was found to have watershed infarcts in the anterior cerebral artery-middle cerebral artery and middle cerebral artery-posterior cerebral artery watershed zones in addition to bilateral caudate infarcts. CONCLUSIONS AND RELEVANCE: Pituitary apoplexy can cause compression of bilateral anterior cerebral arteries from the expanding mass and lead to bilateral caudate infarcts. It is important to understand the pathophysiology of cerebral ischemia in pituitary apoplexy to improve management.

Decreased caudate response to milkshake is associated with higher body mass index and greater impulsivity.

Previous investigations consistently report a negative association between body mass index (BMI) and response in the caudate nucleus during the consumption of palatable and energy dense food. Since this response has also been linked to weight gain, we sought to replicate this finding and determine if the reduced response is associated with measures of impulsivity or food reward. Two studies were conducted in which fMRI was used to measure brain response to milkshake and a tasteless control solution. In Study 1 (n=25) we also assessed self-reported impulsivity, willingness to work for food, and subjective experiences of the pleasantness of milkshake taste and aroma. Replicating prior work, we report a negative association between BMI and brain response to milkshake vs. tasteless in the caudate nucleus. The opposite pattern was observed in the ventral putamen, with greater response observed in the 13 overweight compared to the 12 healthy weight subjects. Regression of brain response against impulsivity and food reward measures revealed one significant association: in the overweight but not healthy weight group self-reported impulsivity was negatively associated with caudate response to milkshake. In Study 2 (n=14), in addition to assessing brain response to milkshake and tasteless solutions subjects completed a go/no-go task outside the scanner. As predicted, we identified an inverse relationship between caudate response to milkshake vs. tasteless and failure to inhibit responses on the no-go trials. We conclude that the inverse correlation between BMI and caudate response to milkshake is associated with impulsivity but not food reward. These findings suggest that response to milkshake in the dorsal striatum may be related to weight gain by promoting impulsive eating behavior.

Beyond cognitive reserve: behavioural reserve hypothesis in Frontotemporal Dementia.

BACKGROUND: The brain reserve hypothesis posits that there are individual differences in the ability to cope with brain pathology, and that brain damage extent and clinical symptoms are not tightly linked. If cognitive reserve hypothesis has been demonstrated in Alzheimer Disease and Frontotemporal Dementia (FTD), no evidence of reserve mechanisms on behavioural disturbances has been corroborated yet. In FTD, distinct behavioural phenotypes may be identified. OBJECTIVE: To test the behavioural reserve hypothesis in behavioural variant FTD (bvFTD). METHODS: As previously demonstrated, bvFTD patients were grouped into four behavioural phenotypes, i.e. "disinhibited", "apathetic", "language", and "aggressive", by means of Confirmatory Factor Analysis on behavioural assessment. Educational achievement was considered as proxy measure of reserve on behavioural disturbances, and cerebral SPECT as an indirect expression of brain pathology. On each group, the effect of education on brain damage was assessed by slope analysis. RESULTS: A specific effect of education attainment on "disinhibited" phenotype was observed, the higher the education, the greater the hypoperfusion in the right inferior frontal gyrus and the left medial frontal gyrus and right caudate (P<0.001). On the other behavioural phenotypes, no effect of education was reported in modulating brain damage. CONCLUSIONS: We suggest that in neurodegenerative diseases the concept of brain reserve might be extended, as compensatory mechanisms are in action not only for cognitive deficits but for behavioural disturbances as well.

Inhibition of pre-ischeamic conditioning in the mouse caudate brain slice by NMDA- or adenosine A1 receptor antagonists.

Evidence suggests that pre-ischeamic conditioning (PIC) offers protection against a subsequent ischeamic event. Although some brain areas such as the hippocampus have received much attention, the receptor mechanisms of PIC in other brain regions are unknown. We have previously shown that 10 min oxygen and glucose deprivation (OGD) evokes tolerance to a second OGD event in the caudate. Here we further examine the effect of length of conditioning event on the second OGD event. Caudate mouse brain slices were superfused with artificial cerebro-spinal fluid (aCSF) bubbled with 95%O(2)/5%CO(2). OGD was achieved by reducing the aCSF glucose concentration and by bubbling with 95%N(2)/5%CO(2). After approximately 5 min OGD a large dopamine efflux was observed, presumably caused by anoxic depolarisation. On applying a second OGD event, 60 min later, dopamine efflux was delayed and reduced. We first examined the effect of varying the length of the conditioning event from 5 to 40 min and found tolerance to PIC increased with increasing duration of conditioning. We then examined the receptor mechanism(s) underlying PIC. We found that pre-incubation with either MK-801 or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) reduced tolerance to the second OGD event. These data suggest that either N-methyl-D-aspartate (NMDA) or adenosine A(1) receptor activation evokes PIC in the mouse caudate.

Quantitative cerebral blood flow mapping and functional connectivity of postherpetic neuralgia pain: a perfusion fMRI study.

This article investigates the effects of postherpetic neuralgia (PHN) on resting-state brain activity utilizing arterial spin labeling (ASL) techniques. Features of static and dynamic cerebral blood flow (CBF) were analyzed to reflect the specific brain response to PHN pain. Eleven consecutive patients suffering from PHN and 11 age- and gender-matched control subjects underwent perfusion functional magnetic resonance imaging brain scanning during the resting state. Group comparison was conducted to detect the regions with significant changes of CBF in PHN patients. Then we chose those regions that were highly correlated with the self-reported pain intensity as "seeds" to calculate the functional connectivity of both groups. Absolute CBF values of these regions were also compared across PHN patients and control subjects. Significant increases in CBF of the patient group were observed in left striatum, right thalamus, left primary somatosensory cortex (S1), left insula, left amygdala, left primary somatomotor cortex, and left inferior parietal lobule. Significant decreases in CBF were mainly located in the frontal cortex. Regional CBF in the left caudate, left insula, left S1, and right thalamus was highly correlated with the pain intensity, and further comparison showed that the regional CBF in these regions is significantly higher in PHN groups. Functional connectivity results demonstrated that the reward circuitry involved in striatum, prefrontal cortex, amygdala, and parahippocampal gyrus and the circuitry among striatum, thalamus, and insula were highly correlated with each element in PHN patients. In addition, noninvasive brain perfusion imaging at rest may provide novel insights into the central mechanisms underlying PHN pain.

Distinct contributions of the caudate nucleus, rostral prefrontal cortex, and parietal cortex to the execution of instructed tasks.

When we behave according to rules and instructions, our brains interpret abstract representations of what to do and transform them into actual behavior. In order to investigate the neural mechanisms behind this process, we devised an fMRI experiment that explicitly isolated rule interpretation from rule encoding and execution. Our results showed that a specific network of regions (including the left rostral prefrontal cortex, the caudate nucleus, and the bilateral posterior parietal cortices) is responsible for translating rules into executable form. An analysis of activation patterns across conditions revealed that the posterior parietal cortices represent a mental template for the task to perform, that the inferior parietal gyrus and the caudate nucleus are responsible for instantiating the template in the proper context, and that the left rostral prefrontal cortex integrates information across complex relationships.

Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals.

HIV-associated neurocognitive disorder remains prevalent in HIV-infected individuals despite effective antiretroviral therapy. As these individuals age, comorbid cerebrovascular disease will likely impact cognitive function. Effective tools to study this impact are needed. This study used diffusion tensor imaging (DTI) to characterize brain microstructural changes in HIV-infected individuals with and without cerebrovascular risk factors. Diffusion-weighted MRIs were obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years, standard deviation = 6 years; 19 males, three females). Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical comparisons accounting for multiple comparisons were made between groups with and without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated with significantly higher MD (false discovery rate (FDR) critical p value = 0.008) and lower FA (FDR critical p value = 0.002) in the caudate and lower FA in the hippocampus (FDR critical p value = 0.004). Pearson correlations were performed between DTI measures in the caudate and hippocampus and age- and education-adjusted composite scores of global cognitive function, memory, and psychomotor speed. There were no detectable correlations between the neuroimaging measures and measures of cognition. In summary, we demonstrate that brain microstructural abnormalities are associated with abnormal glucose metabolism in the caudate and hippocampus of HIV-infected individuals. Deep gray matter structures and the hippocampus may be vulnerable in subjects with comorbid abnormal glucose metabolism, but our results should be confirmed in further studies.

Caudate infarcts and hemorrhages.

The caudate nucleus (CN) is composed of a head, body and tail. The head of the CN contributes to forming the floor of the lateral ventricle frontal horn. Moreover, the head, which is medially separated by the septum pellucidum extends beyond the anterior part of the thalamus, stroking the telencephalic cortex. The superior part of the head is covered by the knee of the corpus callosum, while the inferior part is below the thalamus and lenticular nucleus, which delimits the internal capsule. CN strokes are classified into hemorrhagic and ischemic. The clinical presentation of CN hemorrhage is often characterized by a clinical presentation mimicking subarachnoid hemorrhage, while clinical features of both ischemic and hemorrhagic strokes included behavioral abnormalities dysarthria, movement disorders, language disturbances and memory loss. Most studies to date that have examined vascular CN pathologies have evidenced good outcomes.

Bilateral caudate nucleus infarction associated with a missing A1 segment.

We describe a case of bilateral caudate nucleus infarction caused by cardioembolic stroke associated with a variant circle of Willis. The patient was an 81-year-old man with atrial fibrillation who presented with a sudden disturbance of consciousness. When he became more alert a few days later, he was abulic with no spontaneous speech or activity. A magnetic resonance imaging scan of the brain revealed cerebral infarction of bilateral caudate nucleus heads and the left frontal lobe. The left A1 segment was absent on 3-dimensional computed tomography angiography. One year later, abulia had completely resolved. Bilateral caudate nucleus infarction with variant circle of Willis is rare.