Special issue: Original articleDisconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems
Section snippets
Principles of organization of fiber pathways in the cerebral cortex
Anatomical investigations of the non-human primate brain reveal that there is a consistent pattern of white matter fiber tracts that emanate from every region of the cerebral cortex (Schmahmann and Pandya, 2006). Neurons within any cortical area give rise to five distinct categories of efferent fibers. These are (1) association fibers, (2) striatal fibers, and a confluence of fibers (the “cord”) that carries (3) commissural fibers, and subcortical (projection) fibers to (4) thalamus, and (5)
Clinical features
Subcortical dementia as a clinical entity was first recognized in progressive supranuclear palsy and Huntington's disease (Albert et al., 1974), characterized by slowness of mental processing, forgetfulness, apathy, and depression. This notion was later expanded when it became apparent that focal subcortical lesions play a role in arousal, attention, mood, motivation, language, memory, abstraction, and visuospatial skills (Cummings and Benson, 1984). Patients with Parkinson's disease experience
Clinical features
In the first detailed account of the behavioral consequences of thalamic hemorrhage, Fisher (1959) described neglect (“modified anosognosia and hemiasomatognosia”), global “dysphasia”, confusion and visual hallucinations. Accounts followed of thalamic dementia from prion diseases (Martin, 1997), and behavioral changes in patients with thalamic tumors (Ziegler et al., 1977, Nass et al., 2000), but these lesions are seldom confined to thalamus. There are four thalamic vascular syndromes that
Reticular thalamic nucleus
This nuclear shell surrounds thalamus and conveys afferents from cerebral cortex. It contributes to synchrony and rhythms of thalamic neuronal activity, and is relevant in the pathophysiology of epilepsy (Huguenard and Prince, 1997), and the neural substrates of consciousness (Llinas and Ribary, 2001).
Intralaminar thalamic nuclei
The paracentral (Pcn), central lateral (CL), centromedian (CM), parafascicular (Pf) and midline nuclei such as paraventricular, rhomboid and reunions play a role in autonomic drive. They receive afferents from brainstem, spinal cord, and cerebellum, and have reciprocal connections with cerebral hemispheres (Brodal, 1981, Jones, 1985). The CM/Pf nuclei are also linked with the basal ganglia in tightly connected functional circuits. A sensorimotor circuit links putamen with CM through the
Limbic thalamic nuclei
The functions of the anterior nuclear group – ventral, medial, and dorsal (AV, AM and AD nuclei), and the lateral dorsal (LD) nucleus, reflect their reciprocal anatomical connections with limbic structures in the cingulate gyrus, hippocampus, parahippocampal formation, entorhinal cortex, retrosplenial cortex, orbitofrontal and medial prefrontal cortices, and with subcortical structures including the mamillary bodies and amygdala (Yakovlev et al., 1960, Locke et al., 1961, Yakovlev and Locke,
Specific sensory thalamic nuclei
The specific sensory nuclei include the medial geniculate nucleus (MGN), lateral geniculate nucleus (LGN), and ventroposterior nuclei (lateral, medial, and inferior – VPL, VPM VPI).
Medial geniculate nucleus connections with primary and association auditory cortices infer a role in higher level auditory processing, as well as in elementary audition (Mesulam and Pandya, 1973, Pandya et al., 1994, Hackett et al., 1998).
The lateral geniculate projects to primary and secondary visual cortices (
Effector thalamic nuclei
Motor nuclei include the ventral anterior (VA), ventromedial (VM), and ventral lateral (VL) nuclei. Subregions within VA receive afferents from the internal globus pallidus (Ilinsky and Kultas-Ilinsky, 1987), are linked with premotor cortices (Jones, 1997), and may be responsible for dystonia in rostral thalamic lesions. Neurons in VA receiving afferents from the substantia nigra pars reticulata (Jones, 1985, Francois et al., 2002) are linked with premotor, supplementary motor (Schell and
Associative thalamic nuclei
The lateral posterior, medial dorsal, and pulvinar nuclei are interconnected with cerebral association areas, and have no peripheral afferents or links with primary sensorimotor cortices.
The lateral posterior (LP) nucleus is reciprocally linked with the posterior parietal (Weber and Yin, 1984, Yeterian and Pandya, 1985, Schmahmann and Pandya, 1990), medial and dorsolateral extrastriate (Yeterian and Pandya, 1997), and posterior cingulate and medial parahippocampal cortices (Yeterian and Pandya,
Thalamic connectional topography
Sensorimotor, effector, limbic, and associative regions of cerebral cortex are therefore linked with distinctly different sets of thalamic nuclei. Thalamic projections to the posterior parietal lobe exemplify this concept (Schmahmann and Pandya, 1990). Connections become progressively elaborated as one moves from rostral to caudal within both the superior and the inferior parietal lobules. Rostral areas concerned with intramodality somatosensory processing are related to modality-specific
Clinical features
The cerebellum is subcortical only in the sense that it is distinct from cerebral cortex. The traditional view that cerebellar function is confined to the coordination of voluntary motor activity has evolved in recent years (Schmahmann, 1997). Evidence from patients has made it plain that cerebellar pathology is related to intellectual and emotional deficits in addition to motor incoordination. The wider role of the cerebellum in nervous system function has far-reaching implications for
Discussion
This overview of the neurology and neuropsychiatry of basal ganglia, thalamus and cerebellum makes it clear that “higher cortical functions” are not exclusively the domain of the cerebral cortex. The principle of organization of cerebral cortex, apparent from tract tracing studies, is that each cortical area has association, striatal, and projection fibers linking it in a precise manner to topographically arranged sectors within other cortical regions and subcortical areas. How does the
Conclusion
We have reviewed anatomical, clinical, and imaging data implicating the thalamus, basal ganglia and cerebellum in cognition and emotion, in addition to their roles in motor control. We consider these clinical phenomena as disconnection syndromes, extending the earlier notions of Wernicke and Geschwind to the subcortical nodes. We introduce a new theoretical framework in which to consider the distributed neural systems, based on general, and specific, principles of anatomical organization, and
Acknowledgements
Supported in part by RO1 MH067980, and the Birmingham Foundation. The assistance of Jason MacMore BA is greatly appreciated.
List of abbreviations+
- AD
- anterior dorsal thalamic nucleus
- AM
- anteromedial thalamic nucleus
- AS
- arcuate sulcus
- Assn
- association fibers
- AV
- anteroventral thalamic nucleus
- CC
- corpus callosum
- CCAS
- cerebellar cognitive affective syndrome
- Cd
- caudate nucleus
- CeM
- central medial thalamic nucleus
- CL
- central lateral thalamic nucleus
- Cl
- claustrum
- Cld
- central lateral dorsal thalamic nucleus
- CM
- centromedian thalamic nucleus
- Comm
- commissural fibers
- CS
- central sulcus
- Csl
- centralis superior lateralis thalamic nucleus
- DM
- medial dorsal thalamic nucleus
- DSI
- diffusion
References (256)
- et al.
MR diffusion tensor spectroscopy and imaging
Biophysical Journal
(1994) Task-dependent role of the cerebellum in motor learning
Progress in Brain Research
(2004)Control of sensory data acquisition
The Cerebellum and Cognition
International Review of Neurobiology
(1997)- et al.
Functional MRI and the study of OCD: from symptom provocation to cognitive–behavioral probes of cortico-striatal systems and the amygdala
Neuroimage
(1996) - et al.
Diagnosis and neuroimaging of acute stroke producing distal arm monoparesis
Journal of Stroke and Cerebrovasular Diseases
(2003) - et al.
What is a disconnection syndrome?
Cortex
(2008) - et al.
The arcuate fasciculus and the disconnection theme in language and aphasia: history and current state
Cortex
(2008) - et al.
A diffusion tensor imaging tractography atlas for virtual in vivo dissections
Cortex
(2008) - et al.
Virtual in vivo interactive dissection of white matter fasciculi in the human brain
NeuroImage
(2002) - et al.
Cerebellar hypoplasia and frontal lobe cognitive deficits in disorders of early childhood
Neuropsychologia
(1997)
Retinal ganglion cells labelled from the pulvinar nucleus in macaque monkeys
Neuroscience
Impaired problem solving in Parkinson's disease: impact of a set-shifting deficit
Neuropsychologia
The basal ganglia and chunking of action repertoires
Neurobiology of Learning and Memory
Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus
Biological Psychiatry
The cerebellar–hypothalamic axis: basic circuits and clinical observations
The Cerebellum and Cognition
International Review of Neurobiology
Neurocognitive correlates of stereotactic thalamotomy and thalamic stimulation in parkinsonian patients
Brain and Cognition
Bases and implications of learning in the cerebellum – adaptive control and internal model mechanism
Progress in Brain Research
Lateral–posterior and pulvinar reaching cells – comparison with parietal area 5a: a study in behaving Macaca nemestrina monkeys
Experimental Brain Research
The ‘subcortical dementia’ of progressive supranuclear palsy
Journal of Neurology Neurosurgery and Psychiatry
Parallel organization of functionally segregated circuits linking basal ganglia and cortex
Annual Review Neuroscience
Cerebrocerebellar communication systems
Physiological Reviews
Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term
Brain
The Comparative Anatomy of the Nervous System of Vertebrates, including Man
The thalamic relations of the caudal inferior parietal lobule and the lateral prefrontal cortex in monkeys: divergent cortical projections from cell clusters in the medial pulvinar nucleus
The Journal of Comparative Neurology
Specialized elements of orbitofrontal cortex in primates
Annals of the New York Academy of Science
Diverse thalamic projections to the prefrontal cortex in the rhesus monkey
The Journal of Comparative Neurology
The Nervous System and Its Constituent Neurones
Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories
Nature
A cerebellar model of timing and prediction in the control of reaching
Neural computation
Thalamic connections of the dorsomedial visual area in primates
The Journal of Comparative Neurology
Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging
Nature Neuroscience
Limbic thalamus: Structure, intrinsic organization, and connections
The behavioural and motor consequences of focal lesions of the basal ganglia in man
Brain
The syndrome of unilateral tuberothalamic artery territory infarction
Stroke
Loss of psychic self-activation with bithalamic infarction: neurobehavioural, CT, MRI and SPECT correlates
Acta Neurologica Scandinavica
Thalamic infarcts: clinical syndromes, etiology, and prognosis
Neurology
Neurological Anatomy in Relation to Clinical Medicine
The corticopontine projection in the rhesus monkey. Origin and principles of organization
Brain
Lateral thalamic infarcts
Archives of Neurology
Caudate infarcts
Archives of Neurology
Paramedian thalamic and midbrain infarct: clinical and neuropathological study
Annals of Neurology
Neurologic, psychiatric and cognitive manifestations in cerebellar agenesis
Neurology
Extensive metabolic and neuropsychological abnormalities associated with discrete infarction of the genu of the internal capsule
Journal of Neurology Neurosurgery and Psychiatry
Pure amnesia after unilateral left polar thalamic infarct: topographic and sequential neuropsychological and metabolic (PET) correlations
Journal of Neurology Neurosurgery and Psychiatry
Tracking neuronal fiber pathways in the living human brain
Proceedings of the National Academy of Sciences of the United States of America
Prediction and preparation, fundamental functions of the cerebellum
Learning and Memory
Correlative Anatomy of the Nervous System
Subcortical dementia. Review of an emerging concept
Archives of Neurology
Chemoarchitectonic subdivisions of the visual pulvinar in monkeys and their connectional relations with the middle temporal and rostral dorsolateral visual areas, MT and DLr
The Journal of Comparative Neurology
Thalamic infarcts
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