Elsevier

Cortex

Volume 44, Issue 8, September 2008, Pages 1037-1066
Cortex

Special issue: Original article
Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems

https://doi.org/10.1016/j.cortex.2008.04.004Get rights and content

Abstract

Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion.

First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes.

We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model enables the formulation and testing of future hypotheses in investigations using evolving magnetic resonance imaging techniques in humans, and in clinical studies in patients with cortical and subcortical lesions.

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

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