Neuroanatomical alterations in higher-order thalamic nuclei of fetuses with Down syndrome.

OBJECTIVES: Down syndrome (DS) is a genetic condition characterized by cognitive disability starting from infancy. Children with DS exhibit deficits in several cognitive domains, including executive function, i.e., a set of cognitive processes that heavily depend on higher-order thalamic nuclei. The goal of this study was to establish whether executive function-related thalamic nuclei of fetuses with DS exhibit neuroanatomical alterations that may contribute to the defects in higher-order control processes seen in children with DS. PATIENTS AND METHODS: In brain sections from fetuses with DS and control fetuses (gestational week 17-22), we evaluated the cellularity in the mediodorsal nucleus (MD), the centromedian nucleus (CM), and the parafascicular nucleus (PF) of the thalamus and the density of proliferating cells in the third ventricle. RESULTS: We found that all three nuclei had a notably reduced cell density. This defect was associated with a reduced density of proliferating cells in the third ventricle, suggesting that the reduced cellularity in the MD, CM, and PF of fetuses with DS was due to neurogenesis impairment. The separate evaluation of projection neurons and interneurons in the MD, CM, and PF showed that in fetuses with DS the density of projection neurons was reduced, with no changes in interneuron density. CONCLUSION: This study provides novel evidence for DS-linked cellularity alterations in the MD, CM, and PF and suggests that altered signal processing in these nuclei may be involved in the impairment in higher-order control processes observed in individuals with DS starting from infancy.

Thalamic nuclei in frontotemporal dementia: Mediodorsal nucleus involvement is universal but pulvinar atrophy is unique to C9orf72.

Thalamic atrophy is a common feature across all forms of FTD but little is known about specific nuclei involvement. We aimed to investigate in vivo atrophy of the thalamic nuclei across the FTD spectrum. A cohort of 402 FTD patients (age: mean(SD) 64.3(8.2) years; disease duration: 4.8(2.8) years) was compared with 104 age-matched controls (age: 62.5(10.4) years), using an automated segmentation of T1-weighted MRIs to extract volumes of 14 thalamic nuclei. Stratification was performed by clinical diagnosis (180 behavioural variant FTD (bvFTD), 85 semantic variant primary progressive aphasia (svPPA), 114 nonfluent variant PPA (nfvPPA), 15 PPA not otherwise specified (PPA-NOS), and 8 with associated motor neurone disease (FTD-MND), genetic diagnosis (27 MAPT, 28 C9orf72, 18 GRN), and pathological confirmation (37 tauopathy, 38 TDP-43opathy, 4 FUSopathy). The mediodorsal nucleus (MD) was the only nucleus affected in all FTD subgroups (16-33% smaller than controls). The laterodorsal nucleus was also particularly affected in genetic cases (28-38%), TDP-43 type A (47%), tau-CBD (44%), and FTD-MND (53%). The pulvinar was affected only in the C9orf72 group (16%). Both the lateral and medial geniculate nuclei were also affected in the genetic cases (10-20%), particularly the LGN in C9orf72 expansion carriers. Use of individual thalamic nuclei volumes provided higher accuracy in discriminating between FTD groups than the whole thalamic volume. The MD is the only structure affected across all FTD groups. Differential involvement of the thalamic nuclei among FTD forms is seen, with a unique pattern of atrophy in the pulvinar in C9orf72 expansion carriers.

Genetic absence epilepsy: Effective connectivity from piriform cortex to mediodorsal thalamus.

OBJECTIVE: The objective of the study was to quantify effective connectivity from the piriform cortex to mediodorsal thalamus, in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). METHODS: Local field potentials (LFPs) were recorded using microelectrode arrays implanted in the mediodorsal thalamus and piriform cortex, in three urethane anesthetized GAERS and three control rats. Screw electrodes were placed in the primary motor cortex to identify epileptiform discharges. We used transfer entropy to measure effective connectivity from piriform cortex to mediodorsal thalamus prior to and during generalized epileptiform discharges. RESULTS: We observed increased theta band effective connectivity from piriform cortex to mediodorsal thalamus, prior to and during epileptiform discharges in GAERS compared with controls. Increased effective connectivity was also observed in beta and gamma bands from the piriform cortex to mediodorsal thalamus, but only during epileptiform discharges. CONCLUSIONS: This preliminary study suggests that increased effective theta connectivity from the piriform cortex to the mediodorsal thalamus may be a feature of the 'epileptic network' associated with genetic absence epilepsy. Our findings indicate an underlying predisposition of this direct pathway to propagate epileptiform discharges in genetic absence epilepsy.

Proteomics of the mediodorsal thalamic nucleus of rats with stress-induced gastric ulcer.

BACKGROUND: Stress-induced gastric ulcer (SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress (RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus (MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied. AIM: To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU. METHODS: Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis. RESULTS: A total of 2853 proteins were identified, and these included 65 dysregulated (31 upregulated and 34 downregulated) proteins (fold change ratio ≥ 1.2). Gene Ontology (GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanism through which RWIS gives rise to SGU. CONCLUSION: Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.

Structural Thalamofrontal Hypoconnectivity Is Related to Oculomotor Corollary Discharge Dysfunction in Schizophrenia.

By predicting sensory consequences of actions, humans can distinguish self-generated sensory inputs from those that are elicited externally. This is one mechanism by which we achieve a subjective sense of agency over our actions. Corollary discharge (CD) signals-"copies" of motor signals sent to sensory areas-permit such predictions, and CD abnormalities are a hypothesized mechanism for the agency disruptions in schizophrenia that characterize a subset of symptoms. Indeed, behavioral evidence of altered CD, including in the oculomotor system, has been observed in schizophrenia patients. A pathway projecting from the superior colliculus to the frontal eye fields (FEFs) via the mediodorsal thalamus (MD) conveys oculomotor CD associated with saccadic eye movements in nonhuman primates. This animal work provides a promising translational framework in which to investigate CD abnormalities in clinical populations. In the current study, we examined whether structural connectivity of this MD-FEF pathway relates to oculomotor CD functioning in schizophrenia. Twenty-two schizophrenia patients and 24 healthy control participants of both sexes underwent diffusion tensor imaging, and a large subset performed a trans-saccadic perceptual task that yields measures of CD. Using probabilistic tractography, we identified anatomical connections between FEF and MD and extracted indices of microstructural integrity. Patients exhibited compromised microstructural integrity in the MD-FEF pathway, which was correlated with greater oculomotor CD abnormalities and more severe psychotic symptoms. These data reinforce the role of the MD-FEF pathway in transmitting oculomotor CD signals and suggest that disturbances in this pathway may relate to psychotic symptom manifestation in patients.SIGNIFICANCE STATEMENT People with schizophrenia sometimes experience abnormalities in a sense of agency, which may stem from abnormal sensory predictions about their own actions. Consistent with this notion, the current study found reduced structural connectivity in patients with schizophrenia in a specific brain pathway found to transmit such sensorimotor prediction signals in nonhuman primates. Reduced structural connectivity was correlated with behavioral evidence for impaired sensorimotor predictions and psychotic symptoms.

Thalamic shape and volume abnormalities in female patients with panic disorder.

The thalamus is believed to play crucial role in processing viscero-sensory information, and regulating the activity of amygdala in patients with panic disorder (PD). Previous functional neuroimaging studies have detected abnormal activation in the thalamus in patients with PD compared with healthy control subjects (HC). Very few studies, however, have investigated for volumetric abnormalities in the thalamus in patients with PD. Furthermore, to the best of our knowledge, no previous study has investigated for shape abnormalities in the thalamus in patients with PD. Twenty-five patients with PD and 25 HC participants (all female) were recruited for the study. A voxel-wise volume comparison analysis and a vertex-wise shape analysis were conducted to evaluate structural abnormalities in the PD patients compared to HC. The patients with PD demonstrated significant gray matter volume reductions in the thalamus bilaterally, relative to the HC. The shape analysis detected significant inward deformation in some thalamic regions in the PD patients, including the anterior nucleus, mediodorsal nucleus, and pulvinar nucleus. PD patients showed shape deformations in key thalamic regions that are believed to play a role in regulating emotional and cognitive functions.

Progressive delayed hemidystonia following clinically mild traumatic brain injury.

A 16-year-old boy presented with progressive left hemidystonia over 3 years. The possibilities of symptomatic hemidystonia due to focal lesions such as infarct (vasculitis), tumours, tuberculoma, arteriovenous malformations or heredodegenerative disorders such as Wilson disease were considered. Imaging showed a peculiar scar involving right basifrontal region extending upto anterior, centromedian and dorsomedial nuclei of thalamus due to blowout fracture of roof of orbit. This scar was responsible for progressive left hemidystonia. On probing the history, it was revealed that patient had sustained a mild traumatic brain injury (mTBI) 3 years ago. Burke-Fahn-Marsden dystonia severity rating scale showed improvement from 19 to 6 after treatment with tablet trihexyphenidyl 16 mg and clonazepam 1 mg. A linear scar reaching upto thalamus due to blowout fracture of roof of orbit following clinically mTBI is unique. Delayed, progressive hemidystonia has been reported following severe head injury, however is less common following clinically mTBI.

Ascending projections of nociceptive neurons from trigeminal subnucleus caudalis: A population approach.

Second-order neurons in trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1) are critical for craniofacial pain processing and project rostrally to terminate in: ventral posteromedial thalamic nucleus (VPM), medial thalamic nuclei (MTN) and parabrachial nuclei (PBN). The contribution of each region to trigeminal nociception was assessed by the number of phosphorylated extracellular signal-regulated kinase-immunoreactive (pERK-IR) neurons co-labeled with fluorogold (FG). The phenotype of pERK-IR neurons was further defined by the expression of neurokinin 1 receptor (NK1). The retrograde tracer FG was injected into VPM, MTN or PBN of the right hemisphere and after seven days, capsaicin was injected into the left upper lip in male rats. Nearly all pERK-IR neurons were found in superficial laminae of Vc-C1 ipsilateral to the capsaicin injection. Nearly all VPM and MTN FG-labeled neurons in Vc-C1 were found contralateral to the injection site, whereas FG-labeled neurons were found bilaterally after PBN injection. The percentage of FG-pERK-NK1-IR neurons was significantly greater (>10%) for PBN projection neurons than for VPM and MTN projection neurons (<3%). pERK-NK1-IR VPM projection neurons were found mainly in the middle-Vc, while pERK-NK1-immunoreactive MTN or PBN projection neurons were found in the middle-Vc and caudal Vc-C1. These results suggest that a significant percentage of capsaicin-responsive neurons in superficial laminae of Vc-C1 project directly to PBN, while neurons that project to VPM and MTN are subject to greater modulation by pERK-IR local interneurons. Furthermore, the rostrocaudal distribution differences of FG-pERK-NK1-IR neurons in Vc-C1 may reflect functional differences between these projection areas regarding craniofacial pain.

Morphological, structural, and functional alterations of the prefrontal cortex and the basolateral amygdala after early lesion of the rat mediodorsal thalamus.

Early postnatal damage to the mediodorsal thalamus (MD) produces deficits in cognition and behavior believed to be associated with early prefrontal cortical maldevelopment. We assessed the role of MD afferents during development on the morphological and functional maturation of the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Sprague-Dawley rat pups (n = 56) received a bilateral electrolytic lesion of the MD or a MD Sham lesion on postnatal day 4. 7 weeks later, all rats were tested in anxiety-related and cognitive paradigms using the elevated plus maze and novel object recognition tests. Following behavioral testing (P70), rats were killed and the baseline expression of C-Fos protein and the number of GABAergic neurons were evaluated in the PFC and the BLA. The dendritic morphology and spine density in the PFC using Golgi-Cox staining was also evaluated. Adult rats with early postnatal bilateral MD damage exhibited disrupted recognition memory and increased anxiety-like behaviors. The lesion also caused a significant diminution of C-Fos immunolabeling and an increase of the number of GABAergic neurons in the PFC. In the BLA, the number of GABAergic neurons was significantly reduced, associated with an increase in C-Fos immunolabeling. Furthermore, in the PFC the lesion induced a significant reduction in dendritic branching and spine density. Our data are consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good animal model to investigate cognitive symptoms associated with schizophrenia.

Medio-dorsal thalamus and confabulations: Evidence from a clinical case and combined MRI/DTI study.

The Medio-Dorsal Nuclei (MDN) including the thalamic magnocellular and parvocellular thalamic regions has been implicated in verbal memory function. In a 77 year old lady, with a prior history of a clinically silent infarct of the left MDN, we observed the acute onset of spontaneous confabulations when an isolated new infarct occurred in the right MDN. The patient and five age-matched healthy subjects underwent Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI). The thalamic lesions were localized by overlapping Morel Thalamic Atlas with structural MRI data. DTI was used to assess: i) white matter alterations (Fractional Anisotropy, FA) within fibers connecting the ischemic areas to cortex; ii) the micro-structural damage (Mean Diffusivity) within the thalamic sub-regions defined by their structural connectivity to the Anterior Cingulate Cortex (ACC) and to the temporal lobes. These target regions were chosen because their damage is considered associated with the appearance of confabulations. Thalamic lesions were localized within the parvocellular regions of the right and left MDNs. The structural connectivity study showed that the fiber tracts, connecting the bilaterally damaged thalamic regions with the frontal cortex, corresponded to the anterior thalamic radiations (ATR). FA within these tracts was significantly lower in the patient as compared to controls. Mean diffusivity within the MDNs projecting to Broadman area (BA) 24, BA25 and BA32 of ACC was significantly higher in the patient than in control group. Mean diffusivity values within the MDN projecting to temporal lobes in contrast were not different between patient and controls. Our findings suggest the involvement of bilateral MDNs projections to ACC in the genesis of confabulations and help provide clarity to the longstanding debate on the origin of confabulations.

Comparing glutamatergic neuron population in the mediodorsal thalamic nucleus of genetic absence epilepsy rats from strasbourg (GAERS) and normal control Wistar rats.

An imbalance between GABAergic inhibition and glutamatergic excitation is suspected to play a role in the genesis of epileptic processes. In the present study we quantified the number of glutamate+ve neurons in the mediodorsal thalamic nucleus (MD) of genetic absence epilepsy rats from Strasbourg (GAERS) and compared these with values for normal Wistar rats. The MD thalamic nucleus was removed from each animal and the glutamatergic neurons were labelled using light-microscopy glutamate immunohistochemistry. The disector method was used to quantify the glutamate+ve neurons in the MD thalamic nucleus of GAERS and Wistar rats. The data were statistically analyzed. In the Wistar animals glutamate+ve neurons formed 89% and in GAERS 92.3% of the total neurons in 1000µm3 of MD thalamic nucleus. In GAERS glutamate+ve neurons showed statistically significant increase in the MD thalamic nucleus compared to Wistar animals. In Wistar animals the glutamate-ve neurons formed 11% and in GAERS 7.7% of the total neurons in 1000µm3 of MD thalamic. No significant difference was observed in glutamate-ve neurons between the two strains. The average diameter of glutamate+ve neurons showed no significance, while glutamate-ve neurons were significant between the two strains. The results of the present study, on genetic absence epilepsy model, GAERS, confirms the role of MD thalamic nucleus in chemically induced absence epilepsy.

Prefrontal cortex stroke induces delayed impairment in spatial memory.

Stroke is the leading cause of long-term disability. Little is known about the effects of stroke on cognitive deficits. The subtle nature of cognition and its respective domains in areas such as working memory and attention can make this difficult to diagnose and treat. We aimed to establish a model of focal ischemia that targets the prefrontal cortex (PFC) and induce memory impairments. Stroke and sham mice were assessed at one and four-weeks post-stroke on various tests: open-field task to assess activity; grid-walk and cylinder task to assess motor impairments; elevated plus maze to assess anxiety; novel-object and object-location recognition tasks to assess memory impairment. Stroke mice in the open-field showed a small increase in activity with no effects on gross motor tasks or anxiety levels (P ≥ 0.05) at one and four-weeks post-stroke. Assessment of stroke mice on the novel object task showed no differences at either one or four-weeks compared to sham mice (P ≥ 0.05). However, assessment of stroke mice on the object-location recognition task revealed a significant (P ≥ 0.05) impairment in spatial memory by four-weeks compared to controls. Further, we show that stroke results in a small decrease in volume of the medial dorsal nucleus of the thalamus (P ≥ 0.05). This is the first evidence that demonstrates stroke to the PFC results in delayed onset impairment in spatial memory, similar to findings in human epidemiological data. We suggest that this model may be a useful tool in assessing potential rehabilitative/cognitive therapies after stroke.

Thalamic amnesia after infarct: The role of the mammillothalamic tract and mediodorsal nucleus.

OBJECTIVE: To improve current understanding of the mechanisms behind thalamic amnesia, as it is unclear whether it is directly related to damage to specific nuclei, in particular to the anterior or mediodorsal nuclei, or indirectly related to lesions of the mammillothalamic tract (MTT). METHODS: We recruited 12 patients with a left thalamic infarction and 25 healthy matched controls. All underwent a comprehensive neuropsychological assessment of verbal and visual memory, executive functions, language, and affect, and a high-resolution structural volumetric MRI scan. Thalamic lesions were manually segmented and automatically localized with a computerized thalamic atlas. As well as comparing patients with controls, we divided patients into subgroups with intact or damaged MTT. RESULTS: Only one patient had a small lesion of the anterior nucleus. Most of the lesions included the mediodorsal (n = 11) and intralaminar nuclei (n = 12). Patients performed worse than controls on the verbal memory tasks, but the 5 patients with intact MTT who showed isolated lesions of the mediodorsal nucleus (MD) only displayed moderate memory impairment. The 7 patients with a damaged MTT performed worse on the verbal memory tasks than those whose MTT was intact. CONCLUSIONS: Lesions in the MTT and in the MD result in memory impairment, severely in the case of MTT and to a lesser extent in the case of MD, thus highlighting the roles played by these 2 structures in memory circuits.

The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination.

Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task.

A stereological study of the mediodorsal thalamic nucleus in Down syndrome.

The total number of neurons and glial cells in the mediodorsal thalamic (MDT) nucleus of four aged females with Down syndrome (DS; mean age 69years) was estimated and compared to six age- and sex-matched controls. The MDT nucleus was delineated on coronal sections, and cell numbers (large and small neurons, oligodendrocytes, and astrocytes) were estimated using the optical fractionator technique. The DS brains had an average of 3.41×10(6) total neurons in the MDT nucleus in contrast to 5.97×10(6) in the controls, with no overlap (2p=0.004), affecting large (projecting) and small (local inhibitory) neurons nearly equally. In contrast, we observed no significant differences in either glial cell population. The cortical structures of the same four DS brains were previously estimated to be half the normal size of controls with a reduction in cell numbers whereas the basal ganglia were unaffected. As DS brains are affected by developmental delay, premature aging, and Alzheimer-like pathology, the finite cause of the reduced number of cells in MDT nucleus cannot be determined; however, these findings provide stereological evidence for a local reduction in neuron numbers in the MDT nucleus, which could affect the cognitive capacity of patients with DS.

Reduced mediodorsal thalamic volume and prefrontal cortical spindle activity in schizophrenia.

BACKGROUND: We recently found marked deficits in sleep spindles, non-rapid eye movement (NREM) sleep oscillations that are generated within the thalamus and then amplified and sustained in the cortex, in patients with schizophrenia compared to both healthy and psychiatric controls. Here, we investigated the thalamic and cortical contributions to these sleep spindle deficits. METHODS: Anatomical volume of interest analysis (i.e., thalamic volumes) and electroencephalogram (EEG) source modeling (i.e., spindle-related cortical currents) were performed in patients with schizophrenia and healthy comparison subjects. FINDINGS: Schizophrenia patients had reduced mediodorsal (MD) thalamic volumes, especially on the left side, compared to healthy controls, whereas whole thalami and lateral geniculate nuclei did not differ between groups. Furthermore, left MD volumes were strongly correlated with the number of scalp-recorded spindles in an anterior frontal region, and cortical currents underlying these anterior frontal spindles were localized in the prefrontal cortex, in Brodmann area (BA) 10. Finally, prefrontal currents at the peak of spindle activity were significantly reduced in schizophrenia patients and correlated with their performance in an abstraction/working memory task. CONCLUSION: Altogether, these findings point to deficits in a specific thalamo-cortical circuitry in schizophrenia, which is associated with some cognitive deficits commonly reported in those patients.

Artery of Percheron infarction as an unusual cause of coma: three cases and literature review.

OBJECTIVE: Stroke due to occlusion of the artery of Percheron (AOP), an uncommon anatomic variant supplying the bilateral medial thalami, may raise diagnostic challenges and cause life-threatening symptoms. Our objective here was to detail the features and outcomes in three patients who required intensive care unit (ICU) admission and to review the relevant literature. METHODS: Description of three cases and literature review based on a 1973-2013 PubMed search. RESULTS: Three patients were admitted to our ICU with sudden-onset coma and respiratory and cardiovascular dysfunctions requiring endotracheal mechanical ventilation. Focal neurological deficits, ophthalmological signs (abnormal light reflexes and/or ocular motility and/or ptosis), and neuropsychological abnormalities were variably combined. Initial CT scan was normal. Cerebral MRI demonstrated bilateral paramedian thalamic infarction, with extension to the cerebral peduncles in two patients. Consciousness improved rapidly and time to extubation was 1-4 days. All three patients were discharged alive from the hospital and two had good 1-year functional outcomes. Similar clinical features and outcomes were recorded in the 117 patients identified in the literature, of whom ten required ICU admission. CONCLUSIONS: Bilateral paramedian thalamic stroke due to AOP occlusion can be life threatening. The early diagnosis relies on MRI with magnetic resonance angiography. Recovery of consciousness is usually rapid and mortality is low, warranting full-code ICU management.

Damage to the dorsomedial thalamic nucleus, central lateral intralaminar thalamic nucleus, and midline thalamic nuclei on the right-side impair executive function and attention under conditions of high demand but not low demand.

This study reports a patient, OG, with a unilateral right-sided thalamic lesion. High resolution 3T magnetic resonance imaging revealed damage to the parvicellular and magnocellular subdivisions of the dorsomedial thalamus (DMT), the central lateral intralaminar nucleus (also known as the paralamellar DMT), the paraventricular and the central medial midline thalamic nuclei. According to the neuropsychological literature, the DMT, the midline and intralaminar thalamic nuclei influence a wide array of cognitive functions by virtue of their modulatory influences on executive function and attention, and this is particularly indicated under conditions of low arousal or high cognitive demand. We explored this prediction in OG, and compared his performance on a range of low and high demand versions of tests that tapped executive function and attention to a group of 6 age- and IQ-matched controls. OG, without exception, significantly under performed on the high-demand attention and executive function tasks, but performed normally on the low-demand versions. These findings extend and refine current understanding of the effects of thalamic lesion on attention and executive function.