Stereotactic Lesion in the Forel's Field H: A 2-Years Prospective Open-Label Study on Motor and Nonmotor Symptoms, Neuropsychological Functions, and Quality of Life in Parkinson Disease

BACKGROUND Stereotactic lesion in the Forel's field H (campotomy) was proposed in 1963 to treat Parkinson disease (PD) symptoms. Despite its rationale, very few data on this approach have emerged. Additionally, no study has assessed its effects on nonmotor symptoms, neuropsychological functions and quality of life. OBJECTIVE To provide a prospective 2-yr assessment of motor, nonmotor, neuropsychological and quality of life variables after unilateral campotomy. METHODS Twelve PD patients were prospectively evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS), the Dyskinesia Rating Scale and the Parkinson's disease quality of life questionnaire (PDQ39) before campotomy, and after 6 and 24 mo. Nonmotor, neuropsychiatric, neuropsychological and quality of life variables were assessed. The impact of PD on global health was also rated. RESULTS A significant reduction in contralateral rest tremor (65.7%, P < .001), rigidity (87.8%, P < .001), bradykinesia (68%, P < .001) and axial symptoms (24.2%, P < .05) in offmedication condition led to a 43.9% reduction in UPSDRS III scores 2 yr after campotomy (P < .001). Gait improved by 31.9% (P < .05) and walking time to cover 7 m was reduced by 43.2% (P < .05). Pain decreased by 33.4% (P < .01), while neuropsychiatric and neuropsychological functions did not change. Quality of life improved by 37.8% (P < .05), in line with a 46.7% reduction of disease impact on global health (P < .001). CONCLUSION A significant 2-yr improvement of motor symptoms, gait performance and pain was obtained after unilateral campotomy without significant changes to cognition. Quality of life markedly improved in parallel with a significant reduction of PD burden on global health.

Input-output organization of inhibitory neurons in the interstitial nucleus of Cajal projecting to the contralateral trochlear and oculomotor nucleus

Neurons in the interstitial nucleus of Cajal (INC) that are known to be involved in eye and head movements are excitatory. We investigated the input-output organization of inhibitory INC neurons involved in controlling vertical saccades. Intracellular recordings were made in INC neurons activated antidromically by stimulation of the contralateral trochlear or oculomotor nucleus, and their synaptic input properties from the superior colliculi (SCs) and the contralateral INC were analyzed in anesthetized cats. Many INC neurons projected to the contralateral trochlear nucleus, Forel's field H, INC, and oculomotor nucleus, and mainly received monosynaptic excitation followed by disynaptic inhibition from the ipsi- and contralateral SCs. After sectioning the commissural connections between the SCs, these neurons received monosynaptic excitation from the ipsilateral medial SC and disynaptic inhibition via the INC from the contralateral lateral SC. Another group of INC neurons were antidromically activated from the contralateral oculomotor nucleus, INC and Forel's field H, but not from the trochlear nucleus, and received monosynaptic excitation from the ipsilateral lateral SC and disynaptic inhibition from the contralateral medial SC. The former group was considered to inhibit contralateral trochlear and inferior rectus motoneurons in upward saccades, whereas the latter was considered to inhibit contralateral superior rectus and inferior oblique motoneurons in downward saccades. The mutual inhibition existed between these two groups of INC neurons for upward saccades on one side and downward saccades on the other. This pattern of input-output organization of inhibitory INC neurons suggests that the basic neural circuits for horizontal and vertical saccades are similar.

Topographic Organization of Excitatory and Inhibitory Commissural Connections in the Superior Colliculi and Their Functional Roles in Saccade Generation

Our electrophysiological study showed that there are topographic connections between excitatory and inhibitory commissural neurons (CNs) in one superior colliculus (SC) and tectoreticular neurons (TRNs) in the opposite SC. To obtain morphological evidence for these topographic commissural connections between the SCs, tracers were injected into various parts of the SC, the inhibitory burst neuron (IBN) area and Forel's field H (FFH), in the cat. Retrogradely labeled CNs were classified into three types according to their somatic areas and identified as GABA-positive or -negative immunohistochemically. Caudal SC injections labeled small GABA-positive CNs (<200 μm2) in the deep layers of the opposite rostral SC. Rostral SC injections mainly labeled medium-sized GABA-negative CNs (200–700 μm2) in the upper intermediate layer of the opposite rostral SC and small GABA-positive CNs in its deeper layers. Lateral SC injections labeled small GABA-positive CNs in the opposite medial SC and mainly medium-sized GABA-negative CNs in its lateral part. Medial SC injections labeled small GABA-positive CNs in the lateral SC and medium-sized GABA-negative CNs in the medial SC. In comparison, TRNs projecting to the FFH or IBN region were large (>700 μm2) and medium-sized. Many of the medium-sized GABA-negative CNs were TRNs projecting to the FFH. These results indicate that mirror-symmetric excitatory pathways link medial to medial (upper field) and lateral to lateral (lower field) parts of the SCs, whereas upper and lower field representations are linked by reciprocal inhibitory pathways in the tectal commissure. These connections presumably play important roles in conjugate upward and downward vertical saccades.

Commissural Mirror-Symmetric Excitation and Reciprocal Inhibition Between the Two Superior Colliculi and Their Roles in Vertical and Horizontal Eye Movements

The functional roles of commissural excitation and inhibition between the two superior colliculi (SCs) are not yet well understood. We previously showed the existence of strong excitatory commissural connections between the rostral SCs, although commissural connections had been considered to be mainly inhibitory. In this study, by recording intracellular potentials, we examined the topographical distribution of commissural monosynaptic excitation and inhibition from the contralateral medial and lateral SC to tectoreticular neurons (TRNs) in the medial or lateral SC of anesthetized cats. About 85% of TRNs examined projected to both the ipsilateral Forel's field H and the contralateral inhibitory burst neuron region where the respective premotor neurons for vertical and horizontal saccades reside. Medial TRNs received strong commissural excitation from the medial part of the opposite SC, whereas lateral TRNs received excitation mainly from its lateral part. Injection of wheat germ agglutinin–horseradish peroxidase into the lateral or medial SC retrogradely labeled many larger neurons in the lateral or medial part of the contralateral SC, respectively. These results indicated that excitatory commissural connections exist between the medial and medial parts and between the lateral and lateral parts of the rostral SCs. These may play an important role in reinforcing the conjugacy of upward and downward saccades, respectively. In contrast, medial SC projections to lateral SC TRNs and lateral SC projections to medial TRNs mainly produce strong inhibition. This shows that regions representing upward saccades inhibit contralateral regions representing downward saccades and vice versa.

Neural Organization of the Pathways From the Superior Colliculus to Trochlear Motoneurons

The neural organization of the pathways from the superior colliculus (SC) to trochlear motoneurons was analyzed in anesthetized cats using intracellular recording and transneuronal labeling techniques. Stimulation of the ipsilateral or contralateral SC evoked excitation and inhibition in trochlear motoneurons with latencies of 1.1–2.3 and 1.1–3.8 ms, respectively, suggesting that the earliest components of excitation and inhibition were disynaptic. A midline section between the two SCs revealed that ipsi- and contralateral SC stimulation evoked disynaptic excitation and inhibition in trochlear motoneurons, respectively. Premotor neurons labeled transneuronally after application of wheat germ agglutinin-conjugated horseradish peroxidase into the trochlear nerve were mainly distributed ipsilaterally in the Forel's field H (FFH) and bilaterally in the interstitial nucleus of Cajal (INC). Consequently, we investigated these two likely intermediaries between the SC and trochlear nucleus electrophysiologically. Stimulation of the FFH evoked ipsilateral mono- and disynaptic excitation and contralateral disynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the ipsilateral SC facilitated FFH-evoked monosynaptic excitation. Stimulation of the INC evoked ipsilateral monosynaptic excitation and inhibition, and contralateral monosynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the contralateral SC facilitated contralateral INC-evoked monosynaptic inhibition. These results revealed a reciprocal input pattern from the SCs to vertical ocular motoneurons in the saccadic system; trochlear motoneurons received disynaptic excitation from the ipsilateral SC via ipsilateral FFH neurons and disynaptic inhibition from the contralateral SC via contralateral INC neurons. These inhibitory INC neurons were considered to be a counterpart of inhibitory burst neurons in the horizontal saccadic system.

Commissural Excitation and Inhibition by the Superior Colliculus in Tectoreticular Neurons Projecting to Omnipause Neuron and Inhibitory Burst Neuron Regions

Previous electrophysiological studies have shown that the commissural connections between the two superior colliculi are mainly inhibitory with fewer excitatory connections. However, the functional roles of the commissural connections are not well understood, so we sought to clarify the physiology of tectal commissural excitation and inhibition of tectoreticular neurons (TRNs) in the “fixation ” and “saccade ” zones of the superior colliculus (SC). By recording intracellular potentials, we identified TRNs by their antidromic responses to stimulation of the omnipause neuron (OPN) and inhibitory burst neuron (IBN) regions and analyzed the effects of stimulation of the contralateral SC on these TRNs in anesthetized cats. TRNs in the caudal SC (saccade neurons) projected to the IBN region, and received mono- or disynaptic inhibition from the entire rostrocaudal extent of the contralateral SC. In contrast, TRNs in the rostral SC projected to the OPN or IBN region and received monosynaptic excitation from the most rostral level of the contralateral SC, and mono- or disynaptic inhibition from its entire rostrocaudal extent. Among the rostral TRNs with commissural excitation, IBN-projecting TRNs also projected to Forel's field H (vertical gaze center), suggesting that they were most likely saccade neurons related to vertical saccades. In contrast, TRNs projecting only to the OPN region were most likely fixation neurons. Most putative inhibitory neurons in the rostral SC had multiple axon branches throughout the rostrocaudal extent of the contralateral SC, whereas excitatory commissural neurons, most of which were rostral TRNs, distributed terminals to a discrete region in the rostral SC.