Historical controversies about the thalamus: from etymology to function

The authors report on and discuss the historical evolution of the 3 intellectual and scientific domains essential for the current understanding of the function of the human thalamus: 1) the identification of the thalamus as a distinct anatomical and functional entity, 2) the subdivision of thalamic gray matter into functionally homogeneous units (the thalamic nuclei) and relative disputes about nuclei nomenclature, and 3) experimental physiology and its limitations.Galen was allegedly the first to identify the thalamus. The etymology of the term remains unknown although it is hypothesized that Galen may have wanted to recall the thalamus of Odysseus. Burdach was the first to clearly and systematically define the thalamus and its macroscopic anatomy, which paved the way to understanding its internal microarchitecture. This structure in turn was studied in both nonhuman primates (Friedemann) and humans (Vogt and Vogt), leading to several discrepancies in the findings because of interspecies differences. As a consequence, two main nomenclatures developed, generating sometimes inconsistent (or nonreproducible) anatomo-functional correlations. Recently, considerable effort has been aimed at producing a unified nomenclature, based mainly on functional data, which is indispensable for future developments. The development of knowledge about macro- and microscopic anatomy has allowed a shift from the first galenic speculations about thalamic function (the "thalamus opticorum nervorum") to more detailed insights into the sensory and motor function of the thalamus in the 19th and 20th centuries. This progress is mostly the result of lesion and tracing studies. Direct evidence of the in vivo function of the human thalamus, however, originates from awake stereotactic procedures only.Our current knowledge about the function of the human thalamus is the result of a long process that occurred over several centuries and has been inextricably intermingled with the increasing accumulation of data about thalamic macro- and microscopic anatomy. Although the thalamic anatomy can currently be considered well understood, further studies are still needed to gain a deeper insight into the function of the human thalamus in vivo

The nuclear configuration and cortical connections of the human thalamus

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49943/1/900830102_ftp.pd

The diencephalon of the mink. I. The nuclear pattern of the dorsal thalamus

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49950/1/900950305_ftp.pd

Studies on the diencephalon of the virginia opossum.

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49929/1/900770304_ftp.pd

Immunotoxin-Mediated Tract Targeting in the Primate Brain: Selective Elimination of the Cortico-Subthalamic “Hyperdirect” Pathway

Using a neuron-specific retrograde gene-transfer vector (NeuRet vector), we established immunotoxin (IT)-mediated tract targeting in the primate brain that allows ablation of a neuronal population constituting a particular pathway. Here, we attempted selective removal of the cortico-subthalamic “hyperdirect” pathway. In conjunction with the direct and indirect pathways, the hyperdirect pathway plays a crucial role in motor information processing in the basal ganglia. This pathway links the motor-related areas of the frontal lobe directly to the subthalamic nucleus (STN) without relay at the striatum. After electrical stimulation in the motor-related areas such as the supplementary motor area (SMA), triphasic responses consisting of an early excitation, an inhibition, and a late excitation are usually detected in the internal segment of the globus pallidus (GPi). Several lines of pharmacophysiological evidence suggest that the early excitation may be derived from the hyperdirect pathway. In the present study, the NeuRet vector expressing human interleukin-2 receptor α-subunit was injected into the STN of macaque monkeys. Then, IT injections were made into the SMA. In these monkeys, single-neuron activity in the GPi was recorded in response to the SMA stimulation. We found that the early excitation was largely reduced, with neither the inhibition nor the late excitation affected. The spontaneous firing rate and pattern of GPi neurons remained unchanged. This indicates that IT-mediated tract targeting successfully eliminated the hyperdirect pathway selectively from the basal ganglia circuitry without affecting spontaneous activity of STN neurons. The electrophysiological finding was confirmed with anatomical data obtained from retrograde and anterograde neural tracings. The present results define that the cortically-driven early excitation in GPi neurons is mediated by the hyperdirect pathway. The IT-mediated tract targeting technique will provide us with novel strategies for elucidating various neural network functions

Prefrontal Cortex Lesions Impair Object-Spatial Integration

How and where object and spatial information are perceptually integrated in the brain is a central question in visual cognition. Single-unit physiology, scalp EEG, and fMRI research suggests that the prefrontal cortex (PFC) is a critical locus for object-spatial integration. To test the causal participation of the PFC in an object-spatial integration network, we studied ten patients with unilateral PFC damage performing a lateralized object-spatial integration task. Consistent with single-unit and neuroimaging studies, we found that PFC lesions result in a significant behavioral impairment in object-spatial integration. Furthermore, by manipulating inter-hemispheric transfer of object-spatial information, we found that masking of visual transfer impairs performance in the contralesional visual field in the PFC patients. Our results provide the first evidence that the PFC plays a key, causal role in an object-spatial integration network. Patient performance is also discussed within the context of compensation by the non-lesioned PFC

Modeling the Impact of Lesions in the Human Brain

Lesions of anatomical brain networks result in functional disturbances of brain systems and behavior which depend sensitively, often unpredictably, on the lesion site. The availability of whole-brain maps of structural connections within the human cerebrum and our increased understanding of the physiology and large-scale dynamics of cortical networks allow us to investigate the functional consequences of focal brain lesions in a computational model. We simulate the dynamic effects of lesions placed in different regions of the cerebral cortex by recording changes in the pattern of endogenous (“resting-state”) neural activity. We find that lesions produce specific patterns of altered functional connectivity among distant regions of cortex, often affecting both cortical hemispheres. The magnitude of these dynamic effects depends on the lesion location and is partly predicted by structural network properties of the lesion site. In the model, lesions along the cortical midline and in the vicinity of the temporo-parietal junction result in large and widely distributed changes in functional connectivity, while lesions of primary sensory or motor regions remain more localized. The model suggests that dynamic lesion effects can be predicted on the basis of specific network measures of structural brain networks and that these effects may be related to known behavioral and cognitive consequences of brain lesions

Auditory brain-stem evoked potentials in cat after kainic acid induced neuronal loss. I. Superior olivary complex

Auditory brain-stem potentials (ABRs) were studied in cats for up to 45 days after kainic acid had been injected unilaterally or bilaterally into the superior olivary complex (SOC) to produce neuronal destruction while sparing fibers of passage and the terminals of axons of extrinsic origin connecting to SOC neurons. The components of the ABR in cat were labeled by their polarity at the vertex (P, for positive) and their order of appearance (the arabic numerals 1, 2, etc.). Component P1 can be further subdivided into 2 subcomponents labeled P1a and P1b. The correspondences we have assumed between the ABR components in cat and man are indicated by providing a Roman numeral designation for the human component in parentheses following the feline notation, e.g., P4 (V). With bilateral SOC destruction, there was a significant and marked attenuation of waves P2 (III), P3 (IV), P4 (V), P5 (VI), and the sustained potential shift (SPS) amounting to as much as 80% of preoperative values. Following unilateral SOC destruction the attenuation of many of these same ABR components, in response to stimulation of either ear, was up to 50%. No component of the ABR was totally abolished even when the SOC was lesioned 100% bilaterally. In unilaterally lesioned cats with extensive neuronal loss (greater than 75%) the latencies of the components beginning at P3 (IV) were delayed to stimulation of the ear ipsilateral to the injection site but not to stimulation of the ear contralateral to the injection. Binaural interaction components of the ABR were affected in proportion to the attenuation of the ABR. These results are compatible with multiple brain regions contributing to the generation of the components of the ABR beginning with P2 (III) and that components P3 (IV), P4 (V), and P5 (VI) and the sustained potential shift depend particularly on the integrity of the neurons of the SOC bilaterally. The neurons of the lateral subdivision (LSO) and the medial nucleus of the trapezoid body (MNTB) of the SOC have a major role in generating waves P3 (IV) and P4 (V)

Human pallidothalamic and cerebellothalamic tracts: anatomical basis for functional stereotactic neurosurgery

Anatomical knowledge of the structures to be targeted and of the circuitry involved is crucial in stereotactic functional neurosurgery. The present study was undertaken in the context of surgical treatment of motor disorders such as essential tremor (ET) and Parkinson’s disease (PD) to precisely determine the course and three-dimensional stereotactic localisation of the cerebellothalamic and pallidothalamic tracts in the human brain. The course of the fibre tracts to the thalamus was traced in the subthalamic region using multiple staining procedures and their entrance into the thalamus determined according to our atlas of the human thalamus and basal ganglia [Morel (2007) Stereotactic atlas of the human thalamus and basal ganglia. Informa Healthcare Inc., New York]. Stereotactic three-dimensional coordinates were determined by sectioning thalamic and basal ganglia blocks parallel to stereotactic planes and, in two cases, by correlation with magnetic resonance images (MRI) from the same brains prior to sectioning. The major contributions of this study are to provide: (1) evidence that the bulks of the cerebellothalamic and pallidothalamic tracts are clearly separated up to their thalamic entrance, (2) stereotactic maps of the two tracts in the subthalamic region, (3) the possibility to discriminate between different subthalamic fibre tracts on the basis of immunohistochemical stainings, (4) correlations of histologically identified fibre tracts with high-resolution MRI, and (5) evaluation of the interindividual variability of the fibre systems in the subthalamic region. This study should provide an important basis for accurate stereotactic neurosurgical targeting of the subthalamic region in motor disorders such as PD and ET