Differential mood changes following basal ganglia vs thalamic lesions

Patients with computed tomographic scan-verified unilateral lesions in the basal ganglia or thalamus were examined for the presence of poststroke mood disorders. Patients with left-sided basal ganglia lesions (mainly in the head of the caudate nucleus) showed a significantly higher frequency and severity of depression, as compared with patients with right-sided basal ganglia or thalamic (left- or right-sided) lesions. Results suggest that damage to biogenic amine pathways and/or frontocaudate projections may play an important role in the modulation of mood.     

The functional connectivity of intralaminar thalamic nuclei in the human basal ganglia

Projections of the centromedian‐parafasicularis neurons of the intralaminar thalamus are major inputs of the striatum. Their functional role in the activity of human basal ganglia (BG) is not well known. The aim of this work was to study the functional connectivity of intralaminar thalamic nuclei with other BG by using the correlations of the BOLD signal recorded during “resting” and a motor task. Intralaminar nuclei showed a marked functional connectivity with all the tested BG, which was observed during “resting” and did not change with the motor task. As regards the intralaminar nuclei, BG connectivity was much lower for the medial dorsal nucleus (a thalamic nucleus bordering the intralaminar nuclei) and for the default mode network (although intralaminar nuclei showed a negative correlation with the default mode network). After the “regression” of intralaminar nuclei activity (partial correlation), the functional connectivity of the caudate and putamen nuclei with other BG decreased (but not with the primary sensorimotor cortex). Present data provide evidence that intralaminar nuclei are not only critical for striatal activity but also for the global performance of human BG, an action involving subcortical BG loops more than cortico‐subcortical loops. The high correlation found between BG suggest that, similarly to that reported in other brain centers, the very‐slow frequency fluctuations are relevant for the functional activity of these centers. Hum Brain Mapp 36:1335–1347, 2015. © 2014 Wiley Periodicals, Inc .     

Subthalamic nucleus lesions alter basal and dopamine agonist stimulated electrophysiological output from the rat basal ganglia

The subthalamic nucleus (STN) is an important link in the "indirect" striatal efferent pathway. To assess its role on basal ganglia output via the substantia nigra pars reticulata (SNr), we monitored the single unit activities of SNr neurons in chloral hydrate-anesthetized rats 5-8 days after bilateral kainic acid lesions (0.75 microg/0.3 microl/side) of the STN. Consistent with loss of an excitatory input, the average basal firing rate of SNr neurons was significantly reduced in STN-lesioned animals. Moreover, the lesions modified the responses of SNr neurons to individual and concurrent stimulation of striatal D1 and D2 receptors. Bilateral striatal infusions of the D1/D2 agonist apomorphine (10 microg/microl/side) into the ventral-lateral striatum (VLS) were previously shown to cause significant increases in SNr cell firing (to 133% of baseline) in normal rats. However, in STN-lesioned rats, identical infusions caused no overall change in SNr activity (mean, 103% of basal rates). Conversely, selective stimulation of striatal D2 receptors by bilateral co-infusion of the D2 agonist quinpirole and the D1 antagonist SCH 23390 that previously caused little change in SNr firing in normal rats significantly inhibited their firing in STN-lesioned rats. Finally, the modest excitatory responses of SNr neurons to selective stimulation of striatal D1 receptors by co-infusions of SKF 82958 with the D2 antagonist YM09151-2 were not altered by lesions of the STN. These results implicate the STN as a mediator of excitatory response of SNr neurons to D2, and mixed D1/D2, dopamine receptor agonists in normal rats, and challenge conventional views on the role of the STN and the "indirect" pathway in regulating dopamine-stimulated output from the SNr.     

Complementary distribution of glutamatergic cerebellar and GABAergic basal ganglia afferents to the rat motor thalamic nuclei

Motor thalamic nuclei, ventral anterior (VA), ventral lateral (VL) and ventral medial (VM) nuclei, receive massive glutamatergic and GABAergic afferents from the cerebellum and basal ganglia, respectively. In the present study, these afferents were characterized with immunoreactivities for glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular glutamate transporter (VGluT)2, and examined by combining immunocytochemistry with the anterograde axonal labeling and neuronal depletion methods in the rat brain. VGluT2 immunoreactivity was intense in the caudodorsal portion of the VA-VL, whereas GAD67 immunoreactivity was abundant in the VM and rostroventral portion of the VA-VL. The rostroventral VA-VL and VM contained two types of GAD67-immunopositive varicosities (large and small), but the caudodorsal VA-VL comprised small ones alone. VGluT2-immunopositive varicosities were much larger in the caudodorsal VA-VL than those in the rostroventral VA-VL and VM. When anterograde tracers were injected into the basal ganglia output nuclei, the vast majority of labeled axon varicosities were large and distributed in the rostroventral VA-VL and VM, showing immunoreactivity for GAD67, but not for VGluT2. Only the large GAD67-immunopositive varicosities were mostly abolished by kainic acid depletion of substantia nigra neurons. In contrast, large to giant axon varicosities derived from the deep cerebellar nuclei were distributed mostly in the caudodorsal VA-VL, displaying VGluT2 immunoreactivity. The VGluT2-positive varicosities disappeared from the core portion of the caudodorsal VA-VL by depletion of cerebellar nucleus neurons. Thus, complementary distributions of large VGluT2- and GAD67-positive terminals in the motor thalamic nuclei are considered to reflect glutamatergic cerebellar and GABAergic basal ganglia afferents, respectively.     

Role of thalamic motor nuclei in bilateral regulation of serotoninergic transmission in cat basal ganglia

The effects of unilateral application of GABA (10(-5) M) into thalamic motor nuclei (ventralis medialis-ventralis lateralis, VM-VL) on 5-HT transmission in basal ganglia were investigated in halothane-anaesthetized cats implanted with several push-pull cannulae. The release of [3H]5-HT continuously synthesized from [3H]tryptophan was estimated in both caudate nuclei (CN), both substantia nigrae (SN) and in the dorsal raphe nucleus (DRN). [3H]5-HT release was decreased in the two CN and in the two SN but was enhanced in the DRN when GABA was applied into the VM-VL. These results indicate that thalamic motor nuclei are involved in a bilateral regulation of serotoninergic transmission in the basal ganglia.     

Unilateral lesions of basal ganglia nuclei in children during myxovirus para-influenzae infection

Unilateral disorders of the basal ganglia in childhood have received little attention. Infections are a rare cause where as infarction is the most common one. We report the case of a 11 year-old boy who presented an acute hemiplegia with hypodense areas limited to the left lenticular, caudate nuclei and internal capsule. Virologic investigations showed a recent infection due to myxovirus para influenzae. Angiography demonstrated no focal vascular disease. The course was favorable with full recovery.     

Impact of surgery targeting the caudal intralaminar thalamic nuclei on the pathophysiological functioning of basal ganglia in a rat model of Parkinson's disease

There is accumulating evidence that the centre median-parafascicular (CM/Pf) complex of the thalamus is implicated in basal ganglia-related movement disorders and notably in Parkinson's disease. However, the impact of the changes affecting CM/Pf on the pathophysiological functioning of basal ganglia in parkinsonian state remains poorly understood. To address this issue, we have examined the effects of excitotoxic lesion of CM/Pf and of 6-hydroxydopamine-induced lesion of nigral dopamine neurons, separately or in association, on gene expression of markers of neuronal activity in the rat basal ganglia (striatal neuropeptide precursors, GAD67, cytochrome oxidase subunit I) by quantitative in situ hybridization histochemistry. CM/Pf lesion prevented the changes produced by the dopamine denervation in the components of the indirect pathway connecting the striatum to the output structures (striatopallidal neurons, globus pallidus, subthalamic nucleus), and among the output structures, in the entopeduncular nucleus. Preliminary data on the effects of deep brain stimulation of CM/Pf in rats with nigral dopamine lesion show that this surgical approach produces efficient anti-akinetic effect associated with partial reversal of the dopamine lesion-induced increase in striatal preproenkephalin A mRNA levels, a marker of the striatopallidal neurons. These data, which provide substrates for the potential of CM/Pf surgery in the treatment of movement disorders, are discussed in comparison with the effects of lesion or deep brain stimulation of the subthalamic nucleus, the currently preferred target for the surgical treatment of PD.     

Effects of thalamic lesion on the bilateral regulation of serotoninergic transmission in rat basal ganglia

Summary Unilateral kainic acid lesion of the rat centromedian-parafascicular complex (CM-PF) of the thalamus induced a decrease in the 5-hydroxyindole acetic acid/5-hydroxytryptamine ratio both in ipsi and contralateral striatum and substantia nigra, and an increase in both ipsi and contralateral frontal cerebral cortex. No change in apparent serotonin turnover was detected in anterior raphe nuclei. Serotonin synthesis, estimated by measuring 5-hydroxytryptophan accumulation after injection of a decarboxylase inhibitor, was not affected by the CM-PF lesion. The possible pathways involved in the control of serotonin transmission by CM-PF are discussed.     

Synaptic reorganization in the feline ventral anterior thalamic nucleus induced by lesions in the basal ganglia.

This report presents the results of quantitative analysis of synaptic coverage of the dendrites of thalamocortical projection neurons in the adult cat ventral anterior thalamic nucleus (VA) and its changes at short (4 days)- and long-term (1 year) survival times after combined unilateral kainic acid lesions in the substantia nigra pars reticularis and entopeduncular nucleus. The study showed that deafferentation induced an increase in the appositional length of the dendrites of GABAergic local circuit neurons along projection neuron dendrites, accompanied by an increase in the number of dendrodendritic synapses. Dendritic or axonic origin of other unusual presynaptic structures at 1 year postlesion could not be established with certainty. All of them displayed some features of growth cones, such as an abundance of tubular and vesicular structures many with electron-dense contents. Projection neuron dendrites postsynaptic to these profiles contained numerous coated vesicles at the same survival time. The findings suggest that (i) the lesioning of the two basal ganglia output structures induces synaptic reorganization in the VA, (ii) this process appears to be active at 1 year after deafferentation, and (iii) all reactive systems display symmetric contacts and positive GAD immunoreactivity suggesting that homotypic remodeling is taking place. Despite the signs of remodeling, the density of presynaptic terminals with symmetric contacts on primary and secondary projection neuron dendrites in the VA remained below the control level at 1 year postlesion suggesting that an imbalance of excitatory and inhibitory inputs on thalamocortical projection neurons may persist for long periods after deafferentation.     

Anterior thalamic nuclei lesions have a greater impact than mammillothalamic tract lesions on the extended hippocampal system

The anterior thalamic nuclei (ATN), mammillary bodies and their interconnecting fiber tract, the mammillothalamic tract (MTT), are important components of an extended hippocampal circuit for episodic memory. In humans, damage to the MTT or ATN in many disorders is associated with severe anterograde amnesia and it is assumed that their influence on memory is functionally equivalent. The relative influence of these two structures on memory has not, however, been assessed explicitly. Here, a direct comparison found that only ATN lesions impaired spatial reference memory in rats. ATN lesions produced more severe deficits on spatial working memory and reduced zif268 expression to a greater degree and in more corticolimbic sites than did MTT lesions. Conversely, MTT lesions reduced NeuN cell counts in all three subregions of the MB to a greater extent than did ATN lesions, so their relative impact cannot be explained by retrograde neuropathology of the MB. Hence ATN injury causes a more critical dysfunction than would be expected by an emphasis on the indirect influence of brainstem inputs to the extended memory system. The greater ATN lesion deficits found here may represent the consequence of disruption to the direct connections of the ATN with both hippocampal and cortical sites.     

Spreading of slow cortical rhythms to the basal ganglia output nuclei in rats with nigrostriatal lesions

A high proportion of neurons in the basal ganglia display rhythmic burst firing after chronic nigrostriatal lesions. For instance, the periodic bursts exhibited by certain striatal and subthalamic nucleus neurons in 6-hydroxydopamine-lesioned rats seem to be driven by the approximately 1 Hz high-amplitude rhythm that is prevalent in the cerebral cortex of anaesthetized animals. Because the striatum and subthalamic nucleus are the main afferent structures of the substantia nigra pars reticulata, we examined the possibility that the low-frequency modulations (periodic bursts) that are evident in approximately 50% nigral pars reticulata neurons in the parkinsonian condition were also coupled to this slow cortical rhythm. By recording the frontal cortex field potential simultaneously with single-unit activity in the substantia nigra pars reticulata of anaesthetized rats, we proved the following. (i) The firing of nigral pars reticulata units from sham-lesioned rats is not coupled to the approximately 1 Hz frontal cortex slow oscillation. (ii) Approximately 50% nigral pars reticulata units from 6-hydroxydopamine-lesioned rats oscillate synchronously with the approximately 1 Hz cortical rhythm, with the cortex leading the substantia nigra by approximately 55 ms; the remaining approximately 50% nigral pars reticulata units behave as the units recorded from sham-lesioned rats. (iii) Periodic bursting in nigral pars reticulata units from 6-hydroxydopamine-lesioned rats is disrupted by episodes of desynchronization of cortical field potential activity. Our results strongly support that nigrostriatal lesions promote the spreading of low-frequency cortical rhythms to the substantia nigra pars reticulata and may be of outstanding relevance for understanding the pathophysiology of Parkinson's disease.     

Sensory stimulation accelerates dopamine release in the basal ganglia

We report herein the modulation of dopamine release in the basal ganglia during peripheral electrical stimulation in animals. The endogenous dopamine release during electrical stimulation was measured in anesthetized cats by positron emission tomography (PET) using the D2 receptor agonist [11C]-raclopride. Binding potential (BP) parametric maps were calculated using a simplified reference region model. The regional dopamine release evoked by electrical stimulation was estimated both by region of interest (ROI) analysis and statistical parametric mapping (SPM 99). Both ROI analysis and statistical parametric mapping showed significant release of endogenous dopamine in the nucleus accumbens and the striatum contralateral to the stimulated side as compared to the resting condition as well as the ipsilateral side. Accordingly, we suggest that the activity of the dopaminergic neurons in the midbrain projecting to the nucleus accumbens and the striatum is modulated by the input from the afferent nerves. This provides an in vivo evidence for the importance of the basal ganglia in the processing of peripheral information required for normal movement. This may also explain the clinically observed sensory system abnormalities in patients with movement disorders.     

Effects of lesions in some basal ganglia nuclei and efferent projections on tremorine-induced limb rigidity in rats

A mechanical apparatus was used to measure in rats the effects of some unilateral basal ganglia lesions on the hind-limb rigidity produced by the cholinomimetic compound, tremorine. A globus pallidus lesion reduced the resting tone and greatly increased rigidity in the contralateral leg. Lesions in the entopeduncular, subthalamic, and accumbens nuclei had no effects on rigidity, although the entopeduncular nucleus lesion reduced resting limb tone. The role of the globus pallidus in rigidity is significant in relation to work in which striatal lesions abolished tremorine-induced rigidity. Some brain regions that receive basal ganglia efferent fibers received a lesion unilaterally. Lesions in the substantia nigra, red nucleus, or pedunculopontine nucleus had no effect on tremorine-induced rigidity. A habenular lesion significantly reduced rigidity in both hind legs. Very pronounced reductions in rigidity occurred after midbrain lesions involving the central periaqueductal grey region and the superior colliculus. The basal ganglia output pathways that may mediate tremorine rigidity are discussed, together with the possibility that the superior colliculus, which has many muscarinic receptors, may be influenced directly by tremorine.     

Chronic nicotine treatment decreases dopamine D2 agonist binding in the rat basal ganglia.

To elucidate possible actions of nicotine on dopamine D2 receptor binding, the effect of chronic continuous (-)nicotine treatment (osmotic pumps s.c., 0.125 mg kg h-2, 14 days) was studied in the binding of [3H]N-propylnorapomorphine ([3H]NPA) and [125I]sulpride in coronal cryostat sections in the rat. Quantitative autoradiography showed that nicotine decreased the binding of [3H]NPA in the basal ganglia, preferentially in the nucleus accumbens and olfactory tubercle. In contrast, [125I]sulpride binding was not affected. Nicotine decreased the KD value of [3H]NPA by 27% and decreased the Bmax value by 17%, using filter-wiped sections. These results indicate that chronic continuous nicotine treatment affects the D2 receptor and that this effect may be involved in the development of nicotine dependence.     

Changes in Fos expression in the rat brain after unilateral lesions of the anterior thalamic nuclei

Activity of the immediate early gene c-fos was compared across hemispheres in rats with unilateral anterior thalamic lesions. Fos protein was quantified after rats performed a spatial working memory test in the radial-arm maze, a task that is sensitive to bilateral lesions of the anterior thalamic nuclei. Unilateral anterior thalamic lesions produced evidence of a widespread hippocampal hypoactivity, as there were significant reductions in Fos counts in a range of regions within the ipsilateral hippocampal formation (rostral CA1, rostral dentate gyrus, 'dorsal' hippocampus, presubiculum and postsubiculum). A decrease in Fos levels was also found in the rostral and caudal retrosplenial cortex but not in the parahippocampal cortices or anterior cingulate cortices. The Fos changes seem most closely linked to sites that are also required for successful task performance, supporting the notion that the anterior thalamus, retrosplenial cortex and hippocampus form key components of an interdependent neuronal network involved in spatial mnemonic processing.     

Outcomes of basal ganglia and thalamic cavernous malformation surgery: A meta-analysis

Surgical resection of basal ganglia (BG) and thalamic cavernous malformations (CMs) has not yet become standardized in the field of neurosurgery due to the eloquent location of these lesions and the relative paucity of literature on the subject. This review presents a consolidation of the available literature on outcomes and complication rates after surgical resection of these lesions. A systematic literature review was performed via PubMed database for articles published between 1985 and 2019. Studies comprising ≥2 patients receiving surgery for BG or thalamic CMs with available follow-up data were included. Pooled data included patient demographics, CM preoperative characteristics, and surgical outcomes Twenty studies comprising 227 patients were included for analysis. Complete resection was achieved in 94.7% (fixed-effects pooled estimate [FE]: 94.9%[91.0%–97.8%]; random-effects pooled estimate [RE]: 90.0%[79.8%–96.9%]), and hemorrhage of incompletely resected CMs occurred in 50% (FE: 55.9%[25.9%–83.6%]; RE: 55.9%[25.9%–83.6%]) of patients. Early morbidity was observed in 24.0% (FE: 24.9%[17.8%–32.6%]; RE: 24.9%[17.8%–32.6%]). At final follow-up, 67.3% (FE: 67.7%[58.8%–76.0%]; RE: 67.8%[52.2%–81.6%]) and 20.6% (FE: 20.6%[13.6%–28.6%]; RE: 20.9%[9.8%–34.9%]) had improvement and stability of preoperative symptoms, respectively. Mortality rate was 1.3% (FE: 2.3%[0.6%–5.1%]; RE: 2.3%[0.6%–5.1%]). Therefore, high cure rates with low rates of postoperative morbidity can be achieved in BG or thalamic CM surgery. Most patients had improved neurological function at final follow-up. Complete resection should be attempted to reduce rates of repeat hemorrhage.     

Catecholamine alterations in basal ganglia after hippocampal lesions

Rats were given sham, cortical, or hippocampal lesions and sacrificed 7 or 28 days following surgery. Levels of norepinephrine, dopamine, and the major dopamine metabolites, 3, 4-dihydroxyphenylacetic acid and homovanillic acid (HVA), were assayed in 3 brain regions. At day 7 there was a decrease in dopamine utilization and a decrease in norepinephrine levels in the nucleus accumbens after hippocampal damage but both of these measures returned to normal levels by day 28. In the neostriatum HVA levels decreased at day 7 after hippocampal damage. The utilization of dopamine in the neostriatum was decreased at day 28 in animals that received neocortical lesions but this was not observed in animals with hippocampal destruction. No effects of any lesion at any day were found in the olfactory tubercle region, the third brain region analyzed. It is thought that the removal of hippocampal and neocortical input to the basal ganglia influences catecholamine function reflected in the loss and subsequent recovery of dopamine utilization.     

The cortical relationships of certain basal ganglia and the cholinergic basal forebrain nuclei

Retrograde cellular degeneration has been found in the basal nucleus of Meynert in macaque monkeys after large lesions of the neocortex, and in the human brain after either hemidecortication or leucotomy. These observations may be relevant to the interpretation of the cellular degeneration in the basal nucleus in Alzheimer's disease.