Human cortex appears to thin during childhood development. However, the underlying microstructural mechanisms are unknown. Using functional magnetic resonance imaging (fMRI), quantitative MRI (qMRI), and diffusion MRI (dMRI) in children and adults, we tested what quantitative changes occur to gray and white matter in ventral temporal cortex (VTC) from childhood to adulthood, and how these changes relate to cortical thinning. T1 relaxation time from qMRI and mean diffusivity (MD) from dMRI provide independent and complementary measurements of microstructural properties of gray and white matter tissue. In face- and character-selective regions in lateral VTC, T1 and MD decreased from age 5 to adulthood in mid and deep cortex, as well as in their adjacent white matter. T1 reduction also occurred longitudinally in children’s brain regions. T1 and MD decreases 1) were consistent with tissue growth related to myelination, which we verified with adult histological myelin stains, and 2) were correlated with apparent cortical thinning. In contrast, in place-selective cortex in medial VTC, we found no development of T1 or MD after age 5, and thickness was related to cortical morphology. These findings suggest that lateral VTC likely becomes more myelinated from childhood to adulthood, affecting the contrast of MR images and, in turn, the apparent gray–white boundary. These findings are important because they suggest that VTC does not thin during childhood but instead gets more myelinated. Our data have broad ramifications for understanding both typical and atypical brain development using advanced in vivo quantitative measurements and clinical conditions implicating myelin.

1. We have studied the sensations evoked by threshold microstimulation (TMS) in the area of the human principal sensory nucleus of the thalamus [ventralis caudalis (Vc)] in patients (n = 11) undergoing stereotactic surgery for the treatment of movement disorders and pain. Preoperatively, patients were trained to describe somatic sensory stimuli using a standard list of descriptors. This same list was used to describe sensations evoked intraoperatively by thalamic microstimulation. Stimulation sites (n = 216) were defined by location within the area where the majority of cells had a reproducible response to innocuous cutaneous stimulation (core region) or in the cellular area posterior and inferior to the core region (posteroinferior region). 2. TMS-evoked sensations were categorized as paresthetic if the descriptors "tingle," "vibration," or "electric current" were chosen by the patient to describe the sensation and as thermal/pain if the descriptors "cool," "warm," "warm and cool," or "pain" were chosen. Thermal/pain sensations were evoked by stimulation in 82% (9/11) of patients and at 19% of sites studied. These results suggest that thalamic microstimulation can evoke thermal/pain sensations reproducibly across patients. 3. Thermal/pain sensations were evoked more frequently by stimulation at sites in the posteroinferior region (30%) than by stimulation at sites in the core region (5%). Nonpainful thermal sensations composed the majority of thermal/pain sensations evoked by stimulation in both the core (80%) and posteroinferior regions (86%). Sites where stimulation evoked pain and nonpainful cool sensations were found anterior to the area where nonpainful warm sensations were evoked. Thermal/pain sensations were evoked at sites located medially near the border between the core and posteroinferior regions. 4. Radiologic techniques were used to determine the presumed nuclear location of stimulation sites. Thermal/pain sensations were evoked less frequently by stimulation in the part of Vc included in the core region than by stimulation in any of the following: the part of Vc included in the posteroinferior region, ventralis caudalis portae nucleus, ventralis caudalis parvocellularis nucleus, or the white matter underlying the ventral nuclear group. 5. The location of the sensation evoked by stimulation [projected field (PF)] varied widely in size. PFs were categorized as large if they involved more than one part of the body (e.g., face and arm) or if they crossed at least one joint proximal to the metacarpophalangeal joint or to the metatarsophalangeal joint. PFs were more frequently large at sites where thermal/pain sensations were evoked by TMS (33%) than at those where paresthesia were evoked (6%).(ABSTRACT TRUNCATED AT 400 WORDS)

Indirect evidence suggests that the thalamus contributes to abnormal movements occurring in patients with dystonia (dystonia patients). The present study tested the hypothesis that thalamic activity contributes to the dystonic movements that occur in such patients. During these movements, spectral analysis of electromyographic (EMG) signals in flexor and extensor muscles of the wrist and elbow exhibited peak EMG power in the lowest frequency band [0-0.78 Hz (mean: 0.39 Hz) dystonia frequency] for 60-85% of epochs studied during a pointing task. Normal controls showed low-frequency peaks for <16% of epochs during pointing. Among dystonia patients, simultaneous contraction of antagonistic muscles (cocontraction) at dystonia frequency during pointing was observed for muscles acting about the wrist (63% of epochs) and elbow (39%), but cocontraction was not observed among normal controls during pointing. Thalamic neuronal signals were recorded during thalamotomy for treatment of dystonia and were compared with those of control patients without motor abnormality who were undergoing thalamic procedures for treatment of chronic pain. Presumed nuclear boundaries of a human thalamic cerebellar relay nucleus (ventral intermediate, Vim) and a pallidal relay nucleus (ventral oral posterior, Vop) were estimated by aligning the anterior border of the principal sensory nucleus (ventral caudal, Vc) with the region where the majority of cells have cutaneous receptive fields (RFs). The ratio of power at dystonia frequency to average spectral power was >2 (P < 0.001) for cells in presumed Vop often for dystonia patients (81%) but never for control patients. The percentage of such cells in presumed Vim of dystonia patients (32%) was not significantly different from that of controls (31%). Many cells in presumed Vop exhibited dystonia frequency activity that was correlated with and phase-advanced on EMG activity during dystonia, suggesting that this activity was related to dystonia. Thalamic somatic sensory activity also differed between dystonia patients and controls. The percentage of cells responding to passive joint movement or to manipulation of subcutaneous structures (deep sensory cells) in presumed Vim was significantly greater in patients with dystonia than in control patients undergoing surgery for treatment of pain or tremor. Dystonia patients had a significantly higher proportion of deep sensory cells responding to movement of more than one joint (26%, 13/52) than did "control" patients (8%, 4/49). Deep sensory cells in patients with dystonia were located in thalamic maps that demonstrated increased representations of parts of the body affected by dystonia. Thus dystonia patients showed increased receptive fields and an increased thalamic representation of dystonic body parts. The motor activity of an individual sensory cell was related to the sensory activity of that cell by identification of the muscle apparently involved in the cell's receptive field. Specifically, we defined the effector muscle as the muscle that, by c...

Tremor that occurs as a result of a cerebellar lesion, cerebellar tremor, is characteristically an intention tremor. Thalamic activity may be related to cerebellar tremor because transmission of some cerebellar efferent signals occurs via the thalamus and cortex to the periphery. We have now studied thalamic neuronal activity in a cerebellar relay nucleus (ventral intermediate-Vim) and a pallidal relay nucleus (ventralis oral posterior-Vop) during thalamotomy in patients with intention tremor and other clinical signs of cerebellar disease (tremor patients). The activity of single neurons and the simultaneous electromyographic (EMG) activity of the contralateral upper extremity in tremor patients performing a pointing task were analyzed by spectral cross-correlation analysis. EMG spectra during intention tremor often showed peaks of activity in the tremor-frequency range (1.9-5.8 Hz). There were significant differences in thalamic neuronal activity between tremor patients and controls. Neurons in Vim and Vop had significantly lower firing rates in tremor patients than in patients undergoing thalamic surgery for pain (pain controls). Other studies have shown that inputs to Vim from the cerebellum are transmitted through excitatory connections. Therefore the present results suggest that tremor in these tremor patients is associated with deafferentation of the thalamus from cerebellar efferent pathways. The thalamic X EMG cross-correlation functions were studied for cells located in Vim and Vop. Neuronal and EMG activity were as likely to be significantly correlated for cells in Vim as for those in Vop. Cells in Vim were more likely to have a phase lag relative to EMG than were cells in Vop. In monkeys, cells in the cerebellar relay nucleus of the thalamus, corresponding to Vim, are reported to lead movement during active oscillations at the wrist. In view of these monkey studies, the present results suggest that cells in Vim are deafferented and have a phase lag relative to tremor that is not found in normal active oscillations. The difference in phase of thalamic spike X EMG activity between Vim and Vop may contribute to tremor because lesions of pallidum or Vop are reported to relieve cerebellar tremor.

Microstructural mechanisms underlying apparent cortical thinning during childhood development are unknown. Using functional, quantitative, and diffusion magnetic resonance imaging in children and adults, we tested if tissue growth (lower T 1 relaxation time and mean diffusivity (MD)) or pruning (higher T 1 and MD) underlies cortical thinning in ventral temporal cortex (VTC). After age 5, T 1 and MD decreased in mid and deep cortex of functionally--defined regions in lateral VTC, and in their adjacent white matter. T 1 and MD decreases were (i) consistent with tissue growth related to myelin proliferation, which we verified with adult postmortem histology and (ii) correlated with apparent cortical thinning. Thus, contrary to prevailing theories, cortical tissue does not thin during childhood, it becomes more myelinated, shifting the gray--white matter boundary deeper into cortex. As tissue growth is prominent in regions with protracted functional development, our data suggest an intriguing hypothesis that functional development and myelination are interlinked.