Dorsolateral Putamen Research Articles

Mechanisms Underlying Dopamine-Mediated Reward Bias in Compulsive Behaviors

Pathological behaviors such as problem gambling or shopping are characterized by compulsive choice despite alternative options and negative costs. Reinforcement learning algorithms allow a computation of prediction error, a comparison of actual and expected outcomes, which updates our predictions and influences our subsequent choices. Using a reinforcement learning model, we show data consistent with the idea that dopamine agonists in susceptible individuals with Parkinson's disease increase the rate of learning from gain outcomes. Dopamine agonists also increase striatal prediction error activity, thus signifying a "better than expected" outcome. Thus, our findings are consistent with a model whereby a distorted estimation of the gain cue underpins a choice bias toward gains.

Chorea in the both lower limbs associated with nonketotic hyperglycemia.

Hemichorea-hemiballism (HC-HB) is a complication of non-ketotic hyperglycemia (NKH); in NKH patients, the frequency of occurrence of HC-HB is greater than that of bilateral chorea. We report the case of a hyperglycemic patient who showed chorea in both the lower limbs. Magnetic resonance imaging (MRI) of the brain revealed high signal intensity on T1-weighted images of the bilateral dorsolateral putamen. The abnormal involuntary movements disappeared after oral administration of haloperidol. Our case report that chorea associated with NKH is correlated with the topography of the basal ganglia.

Brain Activation Associated With Changes in Heart Rate, Heart Rate Variability, and Plasma Catecholamines During Rectal Distention

To test the hypothesis that gut stimulation provokes autonomic arousal via activation of regional cerebral cortices. How the human brain processes interoceptive signals and forms initial autonomic arousal is one of the key questions to be answered in research on emotion. Twelve healthy males participated in this study. A barostat bag was inserted in the rectum and intermittently inflated with 0, 20, or 40 mm Hg at random for 80 seconds. H(2)(15)O positron emission tomography (PET) of the brain, electrocardiography, and blood sampling for catecholamines were performed. Changes in regional cerebral blood flow were interpreted using statistical parametric mapping. Rectal distention with 40 mm Hg induced a significant increase in heart rate, low frequency (LF)/high frequency (HF) ratio of heart rate variability, and plasma adrenaline. Activated brain areas that were associated with increased heart rate during rectal distention were the right insula, right operculum, right dorsolateral prefrontal cortex, putamen, thalamus, periaqueductal gray, and cerebellum (p < .001, uncorrected), whereas those that were associated with an increased LF/HF ratio were the bilateral insula, putamen, thalamus, midbrain, pons, and cerebellum (p < .001, uncorrected). Activated brain areas that were associated with increased plasma adrenaline were the right insula, right orbitofrontal cortex, right parahippocampal gyrus, putamen, thalamus, periaqueductal gray, pons, and cerebellum (p < .001, uncorrected). Our results suggest that the right insula and the related body mapping regions may form the functional module of sympathetic arousal in response to gut stimulation.

A specific role for posterior dorsolateral striatum in human habit learning

Habits are characterized by an insensitivity to their consequences and, as such, can be distinguished from goal-directed actions. The neural basis of the development of demonstrably outcome-insensitive habitual actions in humans has not been previously characterized. In this experiment, we show that extensive training on a free-operant task reduces the sensitivity of participants' behavior to a reduction in outcome value. Analysis of functional magnetic resonance imaging data acquired during training revealed a significant increase in task-related cue sensitivity in a right posterior putamen-globus pallidus region as training progressed. These results provide evidence for a shift from goal-directed to habit-based control of instrumental actions in humans, and suggest that cue-driven activation in a specific region of dorsolateral posterior putamen may contribute to the habitual control of behavior in humans.

Rehabilitation of gesture imitation: A case study with fMRI

Acquired disorders of gesture imitation are amenable to treatment, but with poor generalisation toward gestures not included in the training program. We investigated the neural basis of this item-specific recovery in a patient with a slowly progressive posterior cortical atrophy, by means of an fMRI study comparing imitation of rehabilitated and not-rehabilitated gestures. Results suggested that in our patient gesture imitation recruited the mirror system and additional areas relevant to gesture analysis and preparation. Imitation of rehabilitated gestures activated the mirror neuron system, and also left dorsolateral prefrontal cortex and putamen, and the right anterior temporal cortex. This suggests that item-specific recovery was based on interaction of circuitry of imitation with neural systems involved in emotional and motivational processing.

Compartmental loss of striatal medium spiny neurons in multiple system atrophy of parkinsonian type

Topographical or compartmental involvement of the putamen and caudate nucleus has not been fully elucidated in multiple system atrophy predominantly presenting with Parkinsonism (MSA-P). We carried out immunohistochemical studies using antibodies to calbindin (CALB) and calcineurin (CaN) as neurochemical markers for striatal medium spiny neurons. We found that in the caudal and dorsolateral putamen, the area most affected in MSA-P, the medium spiny neurons positive for CALB were severely depleted, while CaN-positive neurons were relatively spared in a mosaic pattern. In the dorsal caudate nucleus, an area less affected in MSA, residual CALB-positive neurons exhibited a compartmentalized distribution that corresponded with the striosomal arrangement visualized by Met-enkephalin immunostaining. Our findings suggest that there is a compartmental difference in the susceptibility of striatal medium spiny neurons to neurodegeneration in MSA-P.

Expression of Mutated Huntingtin Fragment in the Putamen Is Sufficient to Produce Abnormal Movement in Non-human Primates

Huntington's disease (HD) is a neurological disorder characterized by striatal degeneration, motor symptoms and complex neuropsychiatric alterations. There is currently no genetic model of HD in non-human primates (NHPs). In this study we investigated neuropathological and behavioral changes following injections of lentiviral vectors encoding a fragment of mutated huntingtin (Htt171-82Q) into the dorsolateral sensorimotor putamen of macaques. In the first study, we injected Htt171-82Q into one hemisphere and a lentiviral vector encoding Htt171-19Q or saline into the other, and studied the animals for 9 weeks. During this period, when apomorphine was administered into Htt171-19Q/82Q animals, it induced progressive chorea, dystonia and ipsilateral turning behavior, whereas animals infected with Htt171-19Q/19Q showed no abnormal behavior. After 9 weeks, the putamen of animals infected with Htt171-82Q presented neuritic and nuclear Htt aggregates, reactive astrocytes and loss of the neuronal marker NeuN. In a second study, we injected Htt171-82Q bilaterally into the dorsolateral putamen. From week 15 after infection, these animals progressively developed spontaneous dyskinesia of the legs, arms, and trunk and, in one case, tics that persisted for up to 30 weeks. The present study constitutes a proof-of-principle for the development of a genetic model of HD in NHP.

T2*-weighted MRI in diagnosis of multiple system atrophy

Putaminal iron deposition is a histopathological feature of multiple system atrophy (MSA), which is not observed in patients with idiopathic Parkinson's disease (PD). T2*-weighted magnetic resonance imaging (MRI) gradient echo (GE) sequences are sensitive for paramagnetic susceptibility changes and therefore may support the clinical differential diagnosis between MSA and PD. We evaluated putaminal signal intensities on 1.0 Tesla scans of 52 MSA patients, 88 patients with PD and 29 healthy control subjects. The typical finding in T2* GE sequences of MSA patients was a signal loss of the dorsolateral putamen, which showed a high specificity (>0.91), but was present in only a subpopulation of patients (sensitivity 0.64-0.69). The combination of the latter with additional presence of a hyperintense lateral rim in fluid attenuated inversion recovery (FLAIR) sequences increased the specificity to 0.97. Using a quantitative evaluation of putaminal signal intensities in defined regions of interest MSA and PD could be discriminated with a diagnostic accuracy (r) of up to 0.82. Although the separation of groups remains incomplete, the use of T2*-weighted GE sequences combined with FLAIR may be helpful for the differential diagnosis of MSA versus PD considering its fast application, easy evaluation, broad availability, the specificity of findings and the presence of putaminal signal loss already at early disease stages.

Progressive increase of frontostriatal brain activation from childhood to adulthood during event‐related tasks of cognitive control

Higher cognitive inhibitory and attention functions have been shown to develop throughout adolescence, presumably concurrent with anatomical brain maturational changes. The relatively scarce developmental functional imaging literature on cognitive control, however, has been inconsistent with respect to the neurofunctional substrates of this cognitive development, finding either increased or decreased executive prefrontal function in the progression from childhood to adulthood. Such inconsistencies may be due to small subject numbers or confounds from age-related performance differences in block design functional MRI (fMRI). In this study, rapid, randomized, mixed-trial event-related fMRI was used to investigate developmental differences of the neural networks mediating a range of motor and cognitive inhibition functions in a sizeable number of adolescents and adults. Functional brain activation was compared between adolescents and adults during three different executive tasks measuring selective motor response inhibition (Go/no-go task), cognitive interference inhibition (Simon task), and attentional set shifting (Switch task). Adults compared with children showed increased brain activation in task-specific frontostriatal networks, including right orbital and mesial prefrontal cortex and caudate during the Go/no-go task, right mesial and inferior prefrontal cortex, parietal lobe, and putamen during the Switch task and left dorsolateral and inferior frontotemporoparietal regions and putamen during the Simon task. Whole-brain regression analyses with age across all subjects showed progressive age-related changes in similar and extended clusters of task-specific frontostriatal, frontotemporal, and frontoparietal networks. The findings suggest progressive maturation of task-specific frontostriatal and frontocortical networks for cognitive control functions in the transition from childhood to mid-adulthood.

Acute Alcohol Withdrawal is Associated with c-Fos Expression in the Basal Ganglia and Associated Circuitry: C57BL/6J and DBA/2J Inbred Mouse Strain Analyses

The DBA/2J (D2) and C57BL/6J (B6) mouse strains are the most widely studied genetic models of severe and mild acute alcohol withdrawal, respectively. Previous studies have identified quantitative trait loci and genes involved in risk for acute ethanol withdrawal using mapping populations derived from the D2 and B6 strains, but the brain region(s) and circuit(s) by which these genes and their protein products influence ethanol physiological dependence and associated withdrawal remain to be elucidated. B6 and D2 were administered a sedative-hypnotic dose of ethanol (4 g/kg) or saline (control) and returned to their home cages where they were left undisturbed for 7 hr, which has been shown in previous studies to correspond to peak acute ethanol withdrawal severity. The mice were then euthanized and assessed for their numbers of c-Fos immunoreactive neurons across 26 brain regions. The question addressed was whether or not ethanol-withdrawn D2 and B6 mice differed in c-Fos induction (neural activation) within circuitry that could explain the severe ethanol withdrawal of the D2 strain and the mild ethanol withdrawal in B6 strain mice. At peak acute ethanol-withdrawal ethanol-withdrawn D2 and B6 mice differed in neural activation within the basal ganglia, including the subthalamic nucleus and the two major output nuclei of the basal ganglia (the medial globus pallidus and the substantia nigra pars reticulata). Genotype-dependent c-Fos induction was also apparent in associated circuitry including the lateral septum, the ventral tegmental area, the nucleus accumbens core, the dorsolateral caudate putamen, the substantia nigra pars compacta, the cingulate and entorhinal cortices, and the ventral pallidum. D2 and B6 mice showed comparable neural activation in the bed nucleus of the stria terminalis, and the nucleus accumbens shell. The present studies are the first to use immediate early gene product expression to assess the pattern of neural activation associated with acute ethanol withdrawal. Our results point to the involvement of an extended basal ganglia circuit in genetically determined differences in acute ethanol withdrawal. Based on these data, we suggest that quantitative trait genes (QTGs) involved in acute ethanol withdrawal exert their effects on this phenotype via one or more of the brain regions and circuits identified. As more information becomes available that integrates neural circuit and QTG analyses, the precise mechanisms by which QTGs affect ethanol physiological dependence and associated withdrawal will become apparent.

Long-range EEG phase synchronization during an arithmetic task indexes a coherent cortical network simultaneously measured by fMRI

An open question lies in whether or not distributed activities in the distant brain regions are integrated into a coherent ensemble for cognitive information processing. Long-range phase synchronization is often observed by scalp EEG measurements during cognitive tasks and is considered to provide a possible neural principle for the functional integration of distributed neural activities. Synchronization could be reflected at the neuron firing level or at the local field potential and could appear in the scalp EEG under certain conditions on neural spatial and temporal coherence. To examine if phase synchronization is concerned with the integration of distant regions, we proposed a method to extract brain activities associated with task-dependent phase synchronization by combining simultaneous fMRI and EEG. By applying this method in a mental arithmetic task, we found a dominant task-dependent increase of phase synchronization around 14 Hz (in beta frequency) across bilateral parietal sites that were associated with both negative and positive BOLD responses. Functional connectivity analyses of these regions demonstrated that an increase in hemispheric beta synchronization was associated with a linking between the cross-hemispheric regions (left angular gyrus and right superior parietal gyrus) and also among the anterior–posterior regions (right dorsolateral prefrontal cortex, putamen, and right superior temporal gyrus). These findings indicate that the positive BOLD regions (dorsolateral prefrontal cortex and superior parietal lobule) are linked with other negative BOLD regions. We also discussed the possible importance of beta synchronization in the formation of a working memory network.

Differentiation of atypical Parkinson syndrome and delineation from idiopathic Parkinson syndrome with routine magnetic resonance tomography

Atrophy of frontal lobe, midbrain, pons, and cerebellum was studied in 16 patients with progressive supranuclear palsy (PSP), 14 with multiple system atrophy of striatonigral type (MSA-P), 20 with idiopathic Parkinson's disease (IPS), and 12 age-matched healthy controls using axial T2-weighted MR images (1.5 Teslar). With <16 mm, the PSP group showed significantly lower anteroposterior midbrain diameters than the IPS, MSA-P, and control groups. We conclude that measurement of the anteroposterior diameter of the midbrain with axial T2-weighted MRI is a useful feature and should be incorporated into the diagnostic criteria for PSP. In addition to the typical slit hyperintensity in margin of putamen and decreased signal intensity in dorsolateral putamen, we found cerebellar atrophy in 64% of patients with MSA-P. Before now, this was considered a typical sign of multiple system atrophy of cerebellar type (MSA-C). The use of this feature in the differential diagnosis of both types of multiple system atrophy is debatable.

Differences in α7 nicotinic acetylcholine receptor binding in motor symptomatic and asymptomatic MPTP-treated monkeys

We studied [ 125I]α-bungarotoxin (btx) binding to α7 nicotinic acetylcholine receptors in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposed macaque monkeys. [ 125I]α-Btx binds throughout the normal monkey brain, with the greatest density in the thalamic nuclei and with moderate to low binding in the hippocampus, prefrontal cortex, caudate, putamen, and substantia nigra. Chronic adminstration of low doses of MPTP resulted in animals with stable cognitive deficits without overt parkinsonian motor symptoms. [ 125I]α-Btx binding in the brains of these animals was significantly increased in the outermost layers of the supplementary motor cortex (area 6M, ~50%), primary motor cortex (area 4, ~112%) and throughout the putamen (~50–72%). In contrast, there was no change in [ 125I]α-btx binding in the brain regions thought to be involved in mediating the cognitive functions impaired in these monkeys (e.g., the hippocampus, areas 9/46D and 46D of the principal sulcus, and area 24c of the cingulate sulcus). Animals with cognitive dysfunction that received escalating doses of MPTP for >6 months developed motor signs of parkinsonism which were indistinguishable from those seen in animals rendered acutely parkinsonian with short term administration of large doses of MPTP. These two “motor symptomatic” groups had significantly increased [ 125I]α-btx binding only in the dorsolateral putamen. Immunohistochemical studies showed that the increased [ 125I]α-btx binding, when observed, was associated with enhanced immunohistochemical staining localized to neurons and was not a result of an astrocytic response to MPTP. These results suggest that the increase in α7 nicotinic acetylcholine receptor expression in the chronic low-dose MPTP treated, motor asymptomatic monkeys may be a part of compensatory processes contributing to the maintained motor functioning in these animals.

Repeated exposure to social stress has long-term effects on indirect markers of dopaminergic activity in brain regions associated with motivated behavior

The visible burrow system (VBS) is a chronic social stress paradigm in which a dominance hierarchy forms among male rats housed with females. Males in the VBS undergo behavioral and physiological changes thought to be manifestations of chronic social stress. Since it is unclear whether chronic social stress affects motivation and reward behavior, brain areas related to these regions were examined. Long-term effects of a single or repeated VBS exposure on mesolimbic subregions were investigated by exposing rats to the VBS either once (one cycle of VBS housing and recovery) or repeatedly (three cycles). Behavior in the VBS was observed and rats were classified as dominants or subordinates. Subordinates were further sub-classified on the basis of stress hormone (corticosterone) response to an acute stressor (i.e. restraint stress). Normal responders were categorized as stress-responsive subordinates (SRS) and animals with a blunted hypothalamic–pituitary–adrenal axis response were designated as non-responsive subordinates (NRS). Controls males were pair-housed with a single female during VBS periods and alone during recovery. Lowered enkephalin-mRNA levels were observed in the nucleus accumbens (Acb) after single VBS exposure in SRS and repeated VBS exposure both subordinate groups (i.e. SRS+NRS) compared with controls. Decreased dopamine transporter density was detected after single VBS exposure in the dorsolateral caudate putamen (DLCPu) of NRS and after repeated VBS exposure in the Acb of NRS compared with controls. Dopamine D2 receptor density was elevated after single VBS exposure in the Acb of both subordinate groups (SRS+NRS) and after repeated VBS exposure in the DLCPu, dorsomedial CPu, and Acb of NRS compared with controls. No changes in dopamine D1 receptor binding were observed in any group. These results suggest that long-term changes in dopamine activity in mesolimbic structures persist after repeated exposures to chronic social stress and may provide insight into the neurochemical basis of depressive illness and subsequent comorbidity with drug abuse vulnerability.

Presynaptic control of striatal dopamine neurotransmission in adult vesicular monoamine transporter 2 (VMAT2) mutant mice.

The vesicular monoamine transporter 2 (VMAT2) plays a pivotal role in regulating the size of vesicular and cytosolic dopamine (DA) storage pools within the CNS, and can thus influence extracellular DA neurotransmission. Transgenic mice have been generated with a dramatically reduced (by approximately 95%) expression of the VMAT2 gene which, unlike complete knockout lines, survive into adulthood. We compared the pre-synaptic regulation of both impulse-dependent (exocytotic) and carrier-mediated (via reversal of the DA transporter, DAT) DA release in the dorsolateral caudate putamen (CPu) of striatal slices derived from adult homozygous VMAT2 mutant and wild-type mice using fast cyclic voltammetry. Impulse-dependent DA release, evoked by a single electrical pulse, was lower in homozygous (116 nm) than wild-type mice (351 nm) indicating smaller vesicular DA stores, an observation supported by the evanescent effect of amfonelic acid (300 nm) in homozygous mice. Amphetamine (2 microm) increased extracellular DA via DAT reversal in both wild-type (by 459 nm) and VMAT2 mutant (by 168 nm, p < 0.01 vs. wild-type) mice. In both cases, the effect was blocked by the DAT inhibitor GBR12935 (1 microm). Simultaneously, amphetamine decreased impulse-dependent DA release, albeit less in homozygous (by 55%) than in wild-type (by 78%) mice. In wild-types, this decrement was largely reversed by GBR12935 but not by the D2/D3 autoreceptor antagonist (-)sulpiride (1 microm). Conversely, in homozygous VMAT2 mutant mice, it was attenuated by (-)sulpiride but not GBR12935. The D2/D3 receptor agonist quinpirole inhibited impulse-dependent DA release with a lower EC50 value in homozygous mice (12 nm) compared with wild-types (34 nm), indicating the compensatory presence of functionally supersensitive release-regulating autoreceptors. However, analysis of DA reuptake kinetics obtained in the absence and presence of DAT blockade (by cocaine and amfonelic acid) revealed only minor differences in DAT functionality. These results demonstrate that impaired vesicular DA storage constrains extracellular DA levels in the dorsolateral CPu whether induced by either impulse-dependent or carrier-mediated mechanisms and that the relative importance of the DAT and terminal autoreceptors as control mechanisms in the actions of amphetamine are reversed in VMAT2 mutant mice.

Changes in AMPA Receptor Binding in an Animal Model of Inborn Paroxysmal Dystonia

Previous pharmacological studies suggested that glutamatergic overactivity contributes to manifestation of dystonic attacks in mutant hamsters (dtsz), a model of idiopathic paroxysmal dystonia in which episodes of dystonia occur in response to stress. In the present study, [3H]AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor binding was determined by autoradiographic analyses in 41 brain (sub)regions of dtsz hamsters under basal conditions, i.e., in the absence of dystonia, and in a group of mutant hamsters that exhibited severe stress-induced dystonic attacks immediately prior to sacrifice. In comparison to nondystonic control hamsters the basal [3H]AMPA binding was significantly higher in the ventromedial and ventrolateral caudate putamen, the anterior cingulate cortex, the hippocampus, and the lateral septum of dystonic brains. During dystonic attacks the [3H]AMPA binding was significantly lower in the dorsomedial, dorsolateral, and posterior caudate putamen; the ventromedial thalamus; and the frontal cortex of mutant hamsters compared with control animals that were exposed to the same external stimulation. The basal increase in AMPA receptor density within limbic structures may contribute to the susceptibility of stress-inducible dystonic episodes in mutant hamsters. Since AMPA receptor activation is known to cause a fast reduction of the affinity and an internalization of postsynaptic AMPA receptors, the latter finding could reflect a glutamatergic overactivity within the striato-thalamo-cortical circuit during the expression of dystonia, which is in line with previous neurochemical and pharmacological data in dtsz hamsters.

Behavioral and Morphological Comparison of Two Nonhuman Primate Models of Huntington’s Disease

OBJECTIVE Huntington’s disease is a progressive neurodegenerative disease characterized by movement disorder, cognitive deterioration, and selective striatal degeneration. No effective treatment exists, and thus stable primate models could aid in the development of novel therapies. METHODS Two primate models of Huntington’s disease were analyzed: bilateral stereotactic intrastriatal injections of quinolinic acid (QA), and daily systemic intramuscular administration of 3-nitropropionic acid (3-NP) for up to 8 weeks in male Cebus apella monkeys. The animals’ behavior was evaluated before, during, and 3 months after administration of the neurotoxin. Magnetic resonance imaging scans of the brain were obtained before and after treatment. RESULTS Frontal cognitive function as evaluated by object retrieval-detour task test demonstrated a marked deterioration in successful responses, with an increase in barrier reaches in both groups. No significant change in performance of fine motor tasks was observed. QA-treated animals displayed hyperactivity at night. Animals in both groups demonstrated abnormal posture, and the 3-NP-treated group showed spontaneous and apomorphine-induced dystonia and dyskinesia. The QA-treated group displayed large areas of increased signal on T2-weighted images in the caudate and putamen bilaterally. Treatment with 3-NP resulted in smaller lesions. Immunohistochemistry and morphometric analyses revealed that both groups had lesions in the striatum. A large area of neuronal loss with glial sparing was observed in the QA-treated group, including the caudate and putamen bilaterally. The 3-NP-treated group displayed smaller lesions restricted to the dorsolateral putamen. CONCLUSION These results suggest that both QA and 3-NP induce behavioral and morphological features that resemble the juvenile and akinetic-rigid variants of Huntington’s disease, with the group with 3-NP-induced lesions displaying smaller lesions and spontaneous dyskinesia.

Connections of the medial posterior parietal cortex (area 7m) in the monkey

The afferent and efferent cortical and subcortical connections of the medial posterior parietal cortex (area 7m) were studied in cebus (Cebus apella) and macaque (Macaca fascicularis) monkeys using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique. The principal intraparietal corticocortical connections of area 7m in both cebus and macaque cases were with the ipsilateral medial bank of the intraparietal sulcus (MIP) and adjacent superior parietal lobule (area 5), inferior parietal lobule (area 7a), lateral bank of the IPS (area 7ip), caudal parietal operculum (PGop), dorsal bank of the caudal superior temporal sulcus (visual area MST), and medial prestriate cortex (including visual area PO and caudal medial lobule). Its principal frontal corticocortical connections were with the prefrontal cortex in the shoulder above the principal sulcus and the cortex in the shoulder above the superior ramus of the arcuate sulcus (SAS), the area purported to contain the smooth eye movement-related frontal eye field (FEFsem) in the cebus monkey by other investigators. There were moderate connections with the cortex in the rostral bank of the arcuate sulcus (purported to contain the saccade-related frontal eye field; FEFsac), supplementary eye field (SEF), and rostral dorsal premotor area (PMDr). Area 7m also had major connections with the cingulate cortex (area 23), particularly the ventral bank of the cingulate sulcus. The principal subcortical connections of area 7m were with the dorsal portion of the ventrolateral thalamic (VLc) nucleus, lateral posterior thalamic nucleus, lateral pulvinar, caudal mediodorsal thalamic nucleus and medial pulvinar, central lateral, central superior lateral, and central inferior intralaminar thalamic nuclei, dorsolateral caudate nucleus and putamen, middle region of the claustrum, nucleus of the diagonal band, zona incerta, pregeniculate nucleus, anterior and posterior pretectal nuclei, intermediate layer of the superior colliculus, nucleus of Darkschewitsch and dorsomedial parvicellular red nucleus (macaque cases only), dorsal, dorsolateral and lateral basilar pontine nuclei, nucleus reticularis tegmenti pontis, locus ceruleus, and superior central nucleus. The findings are discussed in terms of the possibility that area 7m contains a "medial parietal eye field" and belongs to a neural network of oculomotor-related structures that plays a role in the control of eye movement.

Exercise increases metabolic capacity in the motor cortex and striatum, but not in the hippocampus

Acute bouts of exercise have been shown to produce transient increases in regional cerebral glucose utilization, oxygen uptake, and cerebral blood flow in motor cortex, striatum, and hippocampus. The purpose of this study was to determine whether or not chronic exercise will cause long-term metabolic plasticity in brain structures activated during physical activity. The activity of cytochrome oxidase (COX), is coupled to the production of ATP, and reflects long-term plasticity in metabolic capacity. The present study examined whether or not 6 months of voluntary exercise would increase COX activity in the striatum, sensorimotor cortex, and three hippocampal subfields. Five-month-old, female Long–Evans hooded rats were randomly assigned to a control or exercise condition. Exercising rats had running wheels attached to their home cages. After the training period, fresh brains were rapidly frozen and sectioned with a cryostat. COX activity was measured using COX histochemical methods and optical densitometry. Rats in the exercise condition had significantly higher optical density in the hindlimb and forelimb motor cortices (18%, P<0.01) and dorsolateral caudate putamen (17%, P<0.01), but not in the ventrolateral caudate putamen or any subfield of the hippocampus. Although exercise is believed to increase neuronal activity in the hippocampus, motor cortex and striatum, only limb representations in the motor cortex and striatum increase bioenergetic capacity after regular exercise.

Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS.

To study the association between the cortical cerebral metabolic rate of glucose (CMRglc), MRI T2-weighted total lesion area (TLA), cognitive dysfunction, and neurologic disability in MS. MRI lesion load is widely used in the clinical evaluation of the MS patient but little is known about the associated changes in cortical activation. Twenty-three patients with clinically definite MS underwent measurements of CMRglc, TLA, motor evoked potentials (MEPs), and cognitive and neurologic disability. CMRglc was calculated using PET and 18-F-deoxyglucose and compared with nine normal control subjects. Reductions in CMRglc (p < 0.01) were found in the cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (Spearman rank correlation coefficient [SRCC] = -0.66, p = 0.001), and rCMRglc correlated with regional lesion load in all cerebral lobes (p < or = 0.05). Global cortical CMRglc and cognitive disability also correlated (SRCC = 0.58, p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance as well as TLA. There was no correlation between CMRglc and neurologic disability (Expanded Disability Status Scale) or MEP. Global and regional cortical CMRglc is reduced significantly in MS patients compared with normal control subjects. Furthermore, the CMRglc reductions correlate with TLA as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on cortical cerebral neural function.