Dissociable contributions of thalamic nuclei to recognition memory: novel evidence from a case of medial dorsal thalamic damage.

The thalamic nuclei are thought to play a critical role in recognition memory. Specifically, the anterior thalamic nuclei and medial dorsal nuclei may serve as critical output structures in distinct hippocampal and perirhinal cortex systems, respectively. Existing evidence indicates that damage to the anterior thalamic nuclei leads to impairments in hippocampal-dependent tasks. However, evidence for the opposite pattern following medial dorsal nuclei damage has not yet been identified. In the present study, we investigated recognition memory in NC, a patient with relatively selective medial dorsal nuclei damage, using two object recognition tests with similar foils: a yes/no (YN) test that requires the hippocampus, and a forced choice corresponding test (FCC) that is supported by perirhinal cortex. NC performed normally in the YN test, but was impaired in the FCC test. Critically, FCC performance was impaired only when the study-test delay period was filled with interference. We interpret these results in the context of the representational-hierarchical model, which predicts that memory deficits following damage to the perirhinal system arise due to increased vulnerability to interference. These data provide the first evidence for selective deficits in a task that relies on perirhinal output following damage to the medial dorsal nuclei, providing critical evidence for dissociable thalamic contributions to recognition memory.

Arousal by stimulation of deep-brain nuclei.

Schiff et al. show that deep-brain stimulation of the unspecific thalamocortical system through certain midline thalamic nuclei produces an alerting effect in a patient in a minimally conscious state. Such nuclei include the central lateral nucleus, paralaminar regions of the median dorsalis, and the posterior-medial aspect of the centromedian/parafascicularis nucleus complex.

Abnormal anterior pretectal nucleus activity contributes to central pain syndrome.

Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. We also demonstrated that these changes are due to suppressed inhibitory inputs from the zona incerta (ZI). The anterior pretectal nucleus (APT) is a diencephalic nucleus that projects on both the PO and ZI, suggesting that it might be involved in the pathophysiology of CPS. Here we test the hypothesis that CPS is associated with abnormal APT activity by recording single units from APT in anesthetized rats with CPS resulting from spinal cord lesions. The firing rate of APT neurons was increased in spinal-lesioned animals, compared with sham-operated controls. This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS.

Severe Neonatal Anaemia, MRI Findings and Neurodevelopmental Outcome.

BACKGROUND AND OBJECTIVE: Severe neonatal anaemia can impair cerebral oxygen supply. Data on long-term outcomes following severe neonatal anaemia are scarce. METHODS: Clinical data and neurodevelopmental outcome of 49 (near) term infants with haemoglobin concentration after birth <6.0 mmol/l were retrospectively collected and analysed. In a subgroup of 28 patients, amplitude-integrated EEG was available and in 25 infants cerebral MRI was obtained. Infants were followed up at 14-35 months of age and assessed with the Griffiths Scale of Mental Development or Bayley Scale of Infant Development. RESULTS: Eighteen patients (37%) died during the neonatal period. In 25 patients MRI was performed. A predominant pattern of injury on MRI was seen in the basal ganglia and thalami in 7 patients (28%), whereas some form of white matter injury was present in 16 (64%) and a combination in 3 (12%). Follow-up data were available for 26 patients (84% of survivors). Formal assessment of neurodevelopmental outcome was performed in 20 of 31 (65%) infants who survived (median age: 19 months, range: 14-35). Sixteen infants (80%) had a developmental quotient appropriate for age in the first 2 years after birth. On motor outcome, 1 patient (5%) scored below average (Z-score -1.10). One patient developed cerebral palsy. CONCLUSION: Early neurodevelopmental outcome in surviving patients with severe neonatal anaemia was within the normal range in the majority of the survivors. MRI showed mild-to-moderate white matter injury in two thirds of the infants. Prospectively collected data with a longer follow-up period are needed.

Effects of excitotoxic thalamic intralaminar nuclei lesions on attention and working memory.

In rats, lesions of the thalamic intralaminar nuclei (ILn) impair measures of working memory, but it is unclear whether alterations of attention contribute to the mnemonic deficits. The present experiment tested the effects of ILn lesions on a two-lever attention task that required discrimination of visual signals and non-signals. Rats were trained presurgically in the task and then received sham surgery or infusions of n-methyl-d-aspartate (NMDA) into the ILn to induce excitotoxic lesions. ILn lesions transiently decreased accurate detection of signals. ILn lesions also increased omissions. Compared to sham-lesioned rats, ILn-lesioned animals were not differentially affected when task demands were increased by presenting a visual distracter. Finally, a retention interval was incorporated into the task to assess whether the lesions affected acquisition of a working memory version of this behavioral paradigm. Unlike sham-lesioned animals, ILn-lesioned rats did not demonstrate a significant improvement in signal detection when a retention interval was introduced. The transient lesion-induced deficits in the attention task suggest that, in rats, the ILn may contribute to aspects of attentional processing, but through neural re-organization or activity in other regions, there is compensation for the loss of ILn functioning. The ILn appear to be necessary for maintaining performance when working memory demands are increased.

Behavioural effects of parafascicular thalamic lesions in an animal model of parkinsonism.

We recently reported that the centromedian-parafascicular thalamic complex (CM-Pf) degenerates in Parkinson's disease and progressive supranuclear palsy. The contribution of such thalamic pathology to disease symptoms has not yet been established. The present study therefore investigated the behavioural impact of lesioning the corresponding thalamic region (termed Pf) on a range of behaviours present in rodents. There were four surgical groups: (1) sham medial forebrain bundle (mfb)+sham Pf, (2) 6-OHDA mfb lesion+sham Pf, (3) sham mfb+NMDA Pf lesion, (4) 6-OHDA+NMDA Pf lesions. Posture, sensory functions and apomorphine-induced rotational asymmetry were assessed before and after each surgery. Other assessments performed including a timed motivational task, grooming behaviours and piloerection. 6-OHDA lesions induced postural (ipsilateral curling and head position biases), sensorimotor (increased latency to respond to tactile stimulation of the contralateral side when eating or grooming) and rotational abnormalities (contralateral circling after apomorphine). The main effects of combined 6-OHDA+Pf lesions were improved performance in a motivational task (decreased latency to retrieve reward) but worsened piloerection, relative to animals with either 6-OHDA or Pf lesions alone. The thalamic zone common to all lesioned animals involved the posterior Pf. Our data suggests that the posterior CM-Pf may be involved in motivational responses and autonomic dysfunction in parkinsonian disorders.

Role of thalamic nuclei in the modulation of Fos expression within the cerebral cortex during hypertonic saline-induced muscle nociception.

It has been proposed that thalamic mediodorsal (MD) and ventromedial (VM) nuclei form thalamic 'nociceptive discriminators' in discrimination of nociceptive afferents, and specifically govern endogenous descending facilitation and inhibition. The present study conducted in rats was to explore the role of thalamic MD and VM nuclei in modulation of cerebral neuronal activities by means of detection of spatiotemporal variations of Fos expression within the cerebral cortex. Following a unilateral intramuscular injection of 5.8% saline into the gastrocnemius muscle, Fos expression within the bilateral, different areas of the cerebral cortex except S2 was significantly increased (P<0.05). Particularly, the increases in Fos expression within the cingulate cortex and the insular cortex occurred at 0.5h, 4h and reached the peak level at 4h, 16h, respectively. Electrolytic lesion of the contralateral thalamic MD and VM nuclei significantly blocked the 5.8% saline intramuscularly induced increases in Fos expression within the bilateral cingulate and insular cortices, respectively. Additionally, the 5.8% saline-induced Fos expression in the cingulate cortex and the insular cortex were dose-dependently attenuated by microinjection of µ-opioid antagonist ß-funaltrexamine hydrochloride into the thalamic MD and VM nuclei. It is suggested that (1) the neural circuits of 'thalamic MD nucleus - cingulate cortex' and 'thalamic VM nucleus - insular cortex' form two distinct pathways in the endogenous control of nociception, (2) mirror or contralateral pain is hypothesized to be related to cross-talk of neuronal activities within the bilateral cerebral cortices modulated by µ-opioid receptors within the thalamic MD and VM nuclei.

Distribution and binding parameters of GABAA receptors in the thalamic nuclei of Macaca mulatta and changes caused by lesioning in the globus pallidus and reticular thalamic nucleus.

Ascending output from the basal ganglia to the primate motor thalamus is carried by GABAergic nigro- and pallido-thalamic pathways, which interact with intrinsic thalamic GABAergic systems represented in primates by local circuit neurons and axons of the reticular thalamic nucleus. Disease-triggered pathological processes in the basal ganglia can compromise any of these pathways either directly or indirectly, yet the effects of basal ganglia lesioning on its thalamic afferent-receiving territories has not been studied in primates. Two GABA(A) receptor ligands, [(3)H]muscimol and [(3)H]flunitrazepam, were used to study the distribution and binding properties of the receptor in intact monkeys, those with kainic acid lesions in the globus pallidus, and those with ibotenic acid lesions in the reticular nucleus using quantitative autoradiographic technique on cryostat sections of fresh frozen brain tissue. In control monkeys the binding affinities for [(3)H]muscimol averaged 50 nM in the thalamic nuclei and 86 nM in the basal ganglia while the binding densities varied (maximum density of binding sites [Bmax] range of 99.4-1000.1 fmol/mg of tissue). Binding affinities and Bmax values for [(3)H]flunitrazepam averaged 2.02 nM and 81-113 fmol/mg of tissue, respectively. Addition of 100-microM GABA increased average affinity to 1.35 nM whereas Bmax values increased anywhere from 1-50% in different nuclei. Zolpidem (100 nM) decreased binding by 68-80%. Bmax values for both ligands were decreased at the two survival times in both medial and lateral globus pallidus implying involvement of both nuclei in the lesion. Statistically significant, 40% decrease (P=0.055) of Bmax for [(3)H]muscimol was observed in the ventral anterior nucleus pars densicellularis (VAdc, the main pallidal projection territory in the thalamus) 1 week after globus pallidus lesioning and a 36% decrease (P=0.017) 4 months post-lesioning. In contrast, [(3)H]flunitrazepam Bmax values in the VAdc of the same animals were increased by 23% (P=0.021) at 1 week and 28% (P=0.005) 4 months postlesion, respectively. One week after the reticular nucleus lesioning, the binding densities of [(3)H]muscimol and [(3)H]flunitrazepam were decreased in the thalamic nuclei receiving projections from the lesioned reticular nucleus sector by approximately 50% (P<0.05) and 10-33% (P<0.05), respectively. The results suggest that different GABA(A) receptor subtypes are associated with different GABAergic systems in the thalamus which react differently to deafferentation.

Selective loss of neurons from the thalamic reticular nucleus following severe human head injury.

The GABAergic neurons of the thalamic reticular nucleus, or nucleus reticularis thalami (RT), have been implicated as important components in attentional processing systems. Neurons in the RT are exquisitely sensitive to degeneration following kainic and domoic acid toxicity, experimental global ischemia, human cardiac arrest, and experimental closed head injury in nonhuman primates. The present study was performed to establish whether the selective loss of human RT neurons occurred following severe head injury. Brains from 37 human nonsurvivors of head injury were examined for evidence of RT neuronal loss. RT lesions in were found in 36 of 37 cases, representing 65 of 73 (89%) of the reticular nuclei examined. The incidence of RT lesions was similar in all age groups: 13 of 14 cases (92.9%) in the pediatric (< or = 16 years) group, 33 of 37 (89.2%) in the young adult (18-45 years) group, and 19 of 22 (86.4%) in the older adult (> 45 years) group. RT lesions were characterized by loss of one fourth to three fourths of the neurons from the region of the nucleus associated with the frontal cortex and thalamic mediodorsal (MD) and ventrolateral (VL) nuclei. Sparing of RT neurons correlated highly with the presence of extensive frontal cortical lesions, suggesting that an intact corticothalamic projection was necessary for RT degeneration following head injury. A pathologic cascade with a prominent excitotoxic component is proposed. The loss of these inhibitory thalamic reticular neurons and the resultant thalamic and neocortical neuronal dysfunctions may underlie some forms of attentional deficits that persist following head injury.

Progressive ratio performance in rats with gustatory thalamus lesions.

To determine whether damage of the gustatory thalamus (the parvicellular region of the ventroposteromedial nucleus) disrupts the perceived value of reinforcing stimuli, the performance of rats with bilateral, electrophysiologically guided, electrolytic lesions of the area was examined in Experiment 1 with a progressive-ratio schedule of reinforcement. Lesioned rats showed normal concentration-dependent changes in break point (an index of the amount of effort a subject will expend to obtain reinforcement) and in consummatory responding (licking) for the sucrose reward. In the reward comparison procedure of Experiment 2, however, the same lesioned rats failed to show morphine-induced suppression of alanine consumption. The results provide no support for the view that the thalamic taste area is involved in the perception of the absolute reinforcing value of gustatory stimuli.

Axonal elongation into peripheral nerve grafts between thalamus and somatosensory cortex of the rat. An experimental model.

After destruction of the thalamocortical projections of one side in 12 adult rats, the ipsilateral thalamic ventrobasal nucleus was connected with the contralateral somatosensory cortex through an autologous peripheral nerve graft. Three months after the implanting procedure, horseradish peroxidase was applied to the transected nerve. Retrograde labeling of cells occurred in all examined animals. Evidence of newly formed thalamocortical connections provides the experimental basis to a model suitable for functional evaluations.

Adrenal function response to chronic stress in rats with anterodorsal thalami nuclei lesions.

The effects of chronic stress (forced immobilization, 15 min/day during 12 days), on the plasma corticosterone and the adrenal catecholamines response in rats with anterodorsal thalami nuclei (ADTN) lesions were studied. In sham lesioned rats, chronic stress produced a significant increase in plasma corticosterone (C), as compared to unstressed animals (p < 0.05). The adrenal C was, however, similar in both groups. There were no differences in plasma C values between unstressed and stressed lesioned rats. The adrenal C content, was significantly lower (P < 0.005) in stressed lesioned rats when compared with unstressed lesioned animals. Adrenal norepinephrine (NE) values, in sham lesioned rats after forced immobilization, were significantly below those found in unstressed sham lesioned ones (P < 0.05). There were no changes in adrenal epinephrine (E) response after forced immobilization. In lesioned rats, NE response to chronic stress showed the opposite pattern to that in sham lesioned ones; the adrenal glands of these animals showed a significant increase in NE content as compared to unstressed lesioned rats (P < 0.01). Similar alterations in the adrenal E concentration were found, post stress values were significantly higher (P < 0.01).

Performance of different synchronization measures in real data: a case study on electroencephalographic signals.

We study the synchronization between left and right hemisphere rat electroencephalographic (EEG) channels by using various synchronization measures, namely nonlinear interdependences, phase synchronizations, mutual information, cross correlation, and the coherence function. In passing we show a close relation between two recently proposed phase synchronization measures and we extend the definition of one of them. In three typical examples we observe that except mutual information, all these measures give a useful quantification that is hard to be guessed beforehand from the raw data. Despite their differences, results are qualitatively the same. Therefore, we claim that the applied measures are valuable for the study of synchronization in real data. Moreover, in the particular case of EEG signals their use as complementary variables could be of clinical relevance.

Auditory neglect after right frontal lobe and right pulvinar thalamic lesions.

Auditory unilateral neglect or extinction to simultaneous stimulation is reported in a right-handed male with a lesion in the right frontal lobe and in the right thalamic pulvinar area. The patient was submitted to stereotactic thalamotomy for a post-traumatic intentional ataxia in the left extremities. He was subjected to repeated tests with dichotic listening to consonant-vowel syllables under three different attentional instructions. He was also tested monaurally with the same stimulus materials as used in the dichotic test. The results showed almost complete extinction of the left ear input during dichotic presentations, despite normal hearing when tested with audiometer screening. The left ear extinction effect was independent of instructions to attend to the left or right ear input. However, during monaural presentation, correct left ear reports increased to about 85%. The results are interpreted as showing an auditory attentional neglect caused by the right frontal and pulvinar lesions.

Medullo adrenal response to lesion of anterodorsal thalamic nuclei in rats.

Anterodorsal thalamic nuclei (ADTN) exert an inhibitory influence on hypophyso-adrenal system (HAS) in rats. With the purpose of evaluating if ADTN are also involved in the control of medullo adrenal activity, experiments were conducted on female rats with bilateral lesion of these nuclei. Thirty days after lesion, plasma epinephrine (E) concentration in lesioned rats was higher than that in sham-lesioned control group (P < 0.02). Meanwhile, adrenal E content was significantly lower in lesioned animals than that found in the control group (P < 0.005). Plasma norepinephrine (NE) values in lesioned rats were not significantly different from those in the control ones, however, there was a significant decrease in adrenal NE when compared to the control one (P < 0.02). Basal values of plasma ACTH and plasma and adrenal corticosterone (C) were signicantly higher than those in sham lesioned rats (P < 0.05; P < 0. 001; P < 0.001 respectively). These findings demonstrate that the ADTN in rats are involved in the regulation of both cortico and medullo adrenal activity.

[Long-term rearrangements of the processing of kinesthetic afferentation at the neuronal level of the cat motor cortex after damage to the ventrolateral thalamic nucleus]. / Dlitel'no tekushchie perestroiki protsessov obrabotki kinesteticheskoi afferentatsii na urovne neironov motornoi kory koshek posle povrezhdeniia ventrolateral'nogo iadra talamusa.

Single-unit recordings from motor cortex (area 4) were obtained in cats and under semichronic experimental conditions before and within various periods (from a week to five months) after the lesion in thalamic nucleus ventralis lateralis (n. VL). Neuronal responses to tactile stimulation of the contralateral forelimb and its passive movement in the wrist joint with the mean speed 170 degrees/s were studied. As it had been already reported by others, the magnitude and time course of averaged response histograms for some neurons, which were evoked by imposed displacements of the forelimb, were related to the velocity and/or acceleration components of the movements. Spontaneous firing and kinematic processing capabilities of motor cortical cells were affected by the lesion. The findings are in agreement with a hypothesis that n. VL is essential for encoding specific kinematic features of angular joint movements. Restoration of kinematic processing by cortical neurons in the course of post-traumatic period was characterized by facilitation of activatory reactions of the area 4 cortical cells to peripheral cutaneous stimulation. Some suggestions are made on the nature of plastic changes which develop in neuronal nets of the motor cortex after the lesion of n. VL.

[Compensatory processes in injury to the associative mediodorsal thalamic nucleus]. / Kompensatornye protsessy pri povrezhdenii assotsiativnogo mediodorsal'nogo iadra talamusa.

Recovery of disturbed generalization function with the help of systemic medical injections following damage of mediodorsal thalamic nucleus was studied in cats. Compensation of generalization function could occur following injections of psychotropic drugs affecting cholinergic brain systems.

[Involvement of the subcortical structures in children with cranio-cerebral injuries]. / Porazhenie podkorkovykh struktur mozga u detei pri cherepno-mozgovoi travme.

From experience in the management of 12 cases the authors discuss the clinical picture and pathogenesis of a special form of craniocerebral trauma in children which is characterized by isolated affection of the subcortical ganglia, internal capsule, and the thalamus in the area supplied by the perforating branches of the middle cerebral artery.

Dendritic morphology changes in neurons from the prefrontal cortex, hippocampus and nucleus accumbens in rats after lesion of the thalamic reticular nucleus.

Several studies in rodents have shown that dysfunctions of the thalamic reticular nucleus (TRN) result in deficits of sensory gating and attentional processes, two core features of schizophrenia. TRN receives inputs from the prefrontal cortex (PFC) and hippocampal formation, two structures which send excitatory projections to the nucleus accumbens (NAcc) and are interconnected with the basolateral amygdala (BLA). Here we determined whether (and which) changes occurred four weeks after a TRN lesion in the dendritic morphology of pyramidal neurons of layers 3 and 5 of the PFC, neurons of ventral and dorsal hippocampus, BLA, and the medium spiny neurons of the NAcc. Dendritic morphology and characteristics were measured by using Golgi-Cox procedure followed by Sholl analysis. We also evaluated the effects of TRN lesion on exploratory behavior assessed by hole-board test and locomotor activity induced by a novel environment. We found that TRN damage induced a reduction in the exploratory behavior measured by hole-board test with neuronal hypotrophy in PFC (layer 5), CA1 ventral hippocampus and NAcc neurons. Taken together, these data suggest that the behavioral and morphological effects of TRN lesion are, at least partially, mediated by limbic subregions with possible consequences for schizophrenia-related behaviors.