L69. Neuroscience - Thalamus

• Human thalamus is a bilateral oval mass of gray matter located under the lateral ventricles, and laterally to the third ventricle.
• It resembles an egg in shape.
• Bilateral thalamic masses are connected by the interthalamic adhesion (massa intermedia) in ~80% of human brains.
• The thalamus is separated ventrally from the hypothalamus by the hypothalamic sulcus.
• Diencephalon structures near the thalamus include the hypothalamus, subthalamus, and epithalamus (habenula & pineal body).
• STR, GP, and the posterior limb of the internal capsule are positioned laterally.
• The thalamus comprises many nuclei, each with connections that reveal its function.
• Ex: the DC-ML system projects to the VPL thalamus, which relays information to the primary somatosensory cortex serving as a somatosensory relay nucleus.
• Lesions of the VPL thalamic area lead to a loss of tactile sensation in the contralateral body.

Thalamic Relay Nuclei and Association Nuclei

• Thalamic relay nuclei project to a specific cortical area: Ventral Posterolateral (VPL), Ventral Posteromedial (VPM), Ventral Anterior (VA), and Ventral Lateral (VL).
• Thalamic association nuclei connect diffusely to multiple cortical & subcortical areas: Anterior (ANT), Dorsomedial (DM), Centromedian-Parafascicular (CM-PF), and Pulvinar (PULV).
• The thalamus is divided along its anterior-posterior axis by the Internal Medullary Lamina (IML), a thin myelinated axon bundle.
• Intralaminar thalamic nuclei are embedded in the IML.
• The External Medullary Lamina: A thin myelinated axon band around the thalamus' lateral surface.
• The Thalamic Reticular Nucleus: Thin cellular layer encasing the anterior and lateral surfaces of the thalamus.
• It is lateral to the External Medullary Lamina and medial to the Posterior Limb of the Internal Capsule.

Thalamocortical Relationships

• VP thalamus relays DC-ML, ALS, and trigeminal sensory information to primary somatosensory cortex (VPL and VPM).
• VL thalamus relays basal ganglia and cerebellar motor information to the primary motor cortex for regulation of voluntary movement.
• VA thalamus relays basal ganglia information to the premotor cortex where motor programs are stored.
• ANT/LD thalamus projects to the Cingulate Cortex (part of Limbic Association Cortex).
• DM thalamus projects to the Prefrontal cortex (PFC), taking input from the PFC and amygdala, relates to Limbic System function.
• LP/PULV receives direct projections from retina and superior colliculus (SC), as well as projections from all parts of the visual cortex.
• Visual cortex input is thought to be the main driver of PULV function, while retina and SC input are secondary.
• PULV projects massively back to parietal-temporal-occipital (PTO) cortices.

Thalamocortical Dysrhythmia

• The basic organization of the thalamocortical system appeared ~400 million years ago.
• Thalamic neurons are fundamentally similar from fish to mammals.
• Thalamocortical rhythmicity is important to the overall function of the cerebral cortex.
• It is regulated by the many thalamic afferents from the spinal cord, brainstem, cerebellum, basal ganglia, and cerebral cortex
• The reticular thalamic nucleus (RTN) is an intrinsic regulator of thalamic firing, receiving information from the cerebral cortex and projecting to all thalamic nuclei to help establish thalamocortical rhythmicity.
• The RTN does not project to the cerebral cortex.
• "Thalamocortical dysrhythmia (TCD)": The development of abnormal oscillations of thalamic rhythmicity due to a large loss or alteration of afferent input to the thalamus.
• VL thalamus is connected to both basal ganglia and the cerebellum; TCD occurs when these regions are disrupted by disease.
• Ventral intermediate (Vim) nucleus: A subregion of the posterior half of the VL thalamus.
• Vim contains cells that have firing rates time-locked with the resting tremors of Parkinson Disease and Essential Tremor.
• Vim has been targeted for deep brain stimulation (DBS) to reduce tremors associated with both diseases.

Cognitive Functions

• ANT thalamic nucleus receives memory information from the hippocampus via projections from the mammillary body (MB) known as mammillothalamic tracts (mtt).
• Damage to the ANT thalamic nucleus, MB, or the mtt results in severe memory deficits with lesions often occurring bilaterally at the midline.
• Korsakoff's psychosis due to thiamine deficiency affects this area.
• DM thalamus is the 2nd largest nucleus of the human thalamus.
• Pulvinar is the largest.
• Damage to PFC secondarily degenerates the DM thalamus (e.g. frontal head trauma).
• The amygdala provides large input to the DM thalamus.
• DM lesions decrease emotional responses (increase passivity).
• PULV is the largest nucleus of the human thalamus thought to have evolved along with the visual system.
• It receives input from the retina, visual cortices, and the superior colliculus, projecting into the parietal-temporal-occipital cortex while serving in visual awareness and in the maintenance of visual attentiveness to a particular (behaviorally relevant) feature in a visual scene.
• Damage to the PULV in humans results in visual attentiveness problems.

Thalamic Hemorrhagic Stroke

• The most common cause of thalamic damage.
• The thalamus is 2nd most prevalent brain region affected by hemorrhagic stroke.
• The thalamus receives an overlapping blood supply from vessels from the posterior communicating and posterior cerebral arteries.
• Four blood supply zones overlap different nuclear groups.
• A vascular accident involving a single irrigation zone can affect multiple functional areas of the thalamus, producing a mixture of symptoms, known as the "great imitator" of other types of strokes.
• Polar Zone: ANT and VA irrigation zone. Infarcts result in a mixture of cognitive & motor disturbances such as disoriented patients showing memory deficits, and executive motor program disturbances (apraxia).
• Thalamo-Perforating Zone: DM and intralaminar thalamus irrigation zone. Infarcts cause decreased arousal and coma (if bilateral).
• Impaired learning & memory, confusion, and disorientation.
• Personality changes. Some patients display increased agitation, others display apathy.
• Thalamo-Geniculate Zone: VP and VL regions Irrigation Zone. Infarcts produce sensory loss (variable extent) of all modalities- especially loss of fine touch and proprioception contralateral to the lesion.
• Patients also show abnormal temperature/pain sensitivity (central post-stroke pain) and variable motor signs (ataxia, chorea, etc) due to VL involvement.
• Posterior Choroid Zone: Caudal CM-PF, and PULV irrigation zone. Infarcts are rare, resulting in visual deficits mixed with sensory and motor dysfunctions, especially with damage spreading to include the post limb of the internal capsule.