The goal of the present study was to determine if the medial agranular cortex (AGm) that is thought to contain the supplementary motor area in the rat receives the pallidothalamocortical pathway. A double labeling paradigm was employed whereby injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the entopeduncular nucleus (EN) were combined with injections of the retrograde tracer cholera toxin subunit B into either the rostral or caudal part AGm in the rat. We found that the pallidothalamic projections occupied a crescent shaped arc within the thalamic ventral anterior-ventral lateral nuclear complex (VAL) and ventral medial nucleus (VM). Additional efferents projected to LD/LP, MD, Pf and CL. Dense projections were also found to LHb. In addition, we found that a wide band of cells extending from rostral thalamus including VAL and VM through caudal thalamus including MD, Po, LD/LP, Pf and CL projected to either the rostral or caudal parts of the AGm. The greatest coincidence of the pallidothalamic efferents and AGm thalamocortical cells was found in VAL and VM where numerous PHA-L varicosities were found in close apposition to CTB labeled cells. Synaptic contacts between VAL thalamocortical neurons and pallidal terminals were verified in the electron microscope. These results demonstrate for the first time the pallidothalamocortical pathway by way of VAL to the AGm in the rat.

The terminals formed by the corticothalamic axons are of two types, small and giant endings. This dual mode of corticothalamic projection has been found to be consistent across species (mouse, rat, cat, monkey) and across systems (visual, auditory, somatosensory and motor). In the monkey, this dual mode of projection has been demonstrated for the motor system in the case of the primary motor cortical area, the supplementary motor area and the caudal part of the dorsal premotor cortex. Based on biotinylated dextran amine anterograde tracing experiments, a similar dual mode of termination morphology was found here for corticothalamic axons originating from the other three distinct sub-divisions of the premotor cortex. Furthermore, the pattern of arrangement of giant endings originating from the premotor cortex was found to be similar to that from the supplementary motor area but different to that from the primary motor cortex.

The goal of the present study was to determine the ascending sources to the pre-supplementary motor area (pre-SMA) in macaque monkeys using multiple labeling techniques. We labeled the pallidothalamic projections using biotinylated dextran amine (BDA) and the cerebellothalamic projections using wheatgerm agglutinin conjugated to horseradish peroxidase. The pre-SMA thalamocortical projections neurons were also labeled using cholera toxin subunit b following identification of the pre-SMA by location, and by movements evoked by intracortical microstimulation. The extent of pre-SMA was later confirmed by identifying characteristics from Nissl cytoarchitecture and SMI-32 immunoreactivity. Thalamic nuclear boundaries were based on Nissl cytoarchitecture, acetylcholinesterase chemoarchitecture and Cat-301 immunoreactivity. Cerebellothalamic afferents were distributed predominantly to ventral lateral posterior nucleus (VLp), including medial and dorsal VLp, while the pallidothalamic afferents projected more rostrally to ventral lateral anterior nucleus (VLa) and ventral anterior nucleus (VA). The pre-SMA thalamocortical projection neurons were primarily found in VA and medial VLp. However, scattered cells were also found in VLa, dorsal VLp, central lateral nucleus (CL) and mediodorsal nucleus (MD). Scattered pre-SMA projecting cells overlapped foci of cerebellar label in medial VLp. Additionally, limited overlap of pre-SMA cells and pallidothalamic labeling was found in caudal VA. These findings suggest that the pre-SMA is uniquely positioned to integrate ascending basal ganglia and cerebellar information after a relay from VA and medial VLp. These anatomical findings are consistent with the recent hypothesis that the pre-SMA acts as the coordinator of visual and motor loops in motor learning [J. Cogn. Neurosci. 13 (2001) 626].

Following earlier stereotactic experiences, we re-explored the possibilities of a therapeutic lesion of the pallidothalamic tract in the fields H1 and H2 of Forel in patients with parkinsonian signs. The physiopathological rationale of the pallidothalamic tractotomy (PTT) is based on the presence in the parkinsonian brain of a state of thalamic overinhibition due to an increased output of the internal pallidum. This causes the development of a thalamocortical dysrhythmia characterized by increased low frequencies in the relevant thalamic and frontal cortical areas. The fields of Forel are strategically placed to control this thalamic overinhibition, as they give passage to the majority of the pallidothalamic fibres. Magnetic resonance- and microelectrode-guided stereotactic PTT was proposed to 21 parkinsonian patients (mean age: 60 ± 10 years; mean Hoehn and Yahr in on-condition: 3.5 ± 1; mean disease duration: 11 ± 5 years). At a follow-up of 14 ± 6 months and in on-medication condition, a significant (P < 0.001) postoperative improvement of the motor part of the UPDRS (64.6%) and of the activities of daily living (ADL; 75.8%) was observed. Rest tremor, on-chorea and rigidity were reduced by 77.9, 92.2 and 82.3%, respectively. Distal and axial hypobradykinesias showed an improvement of 72.9 and 64%, respectively. Gait and postural stability also improved (57.5 and 66%, respectively) but at a lower level of significance (P < 0.005). Voice was not statistically influenced. L-dopa intake was decreased by 52.2% (P < 0.001) and 33% of the patients could be freed from treatment. In conclusion, PTT is an effective treatment for chronic therapy-resistant Parkinson's disease, improving symptoms in both on- and off-conditions.