The essential role of the cerebellum in eyeblink classical conditioning in non-human mammals is well documented, and in animals we reported high correlations between Purkinje cell number and associative learning. In elderly humans we found a dramatic relationship between cerebellar volume corrected for total cranial volume and conditioned response (CR) percentage. Neither hippocampal nor total cerebral volume correlated with conditioning. In the present study, anatomical (volumetric) brain magnetic resonance imaging (MRI), delay eyeblink conditioning, and neuropsychological testing were carried out in adults ranging in age from 24 to 87 years. The inclusion of younger adult subjects' cerebellar volume and conditioning performance maintained the very strong relationship between cerebellar volume and associative learning (r = .82; p < .005). Because of the magnitude of Purkinje cells and their dendritic arbor, it is likely that the documented smaller volume of the older adult cerebellum is associated with sh...

BACKGROUND: Nausea is a common and unpleasant GI-associated sensation. While different from pain, nausea also elicits autonomic response and is potentially modulated by specific brain regions. AIMS: To interrogate the neural correlates of nausea in heal...

There is evidence of superior motor outcome improvement when surgical interventions for treating motor symptoms of Parkinson’s disease (PD) are performed within the posterior subthalamic area, particularly at a white matter region called prelemniscal ra...

The dopaminergic system has been shown to be involved in the processing of rewarding stimuli, specifically of errors in reward prediction, in animal studies as well as in recent neuroimaging studies in humans. Furthermore, a specific role of dopamine in the human homolog of the rostral cingulate motor area (rCMA) was proposed in a recent model of error detection. Negative feedback as well as self-detected errors elicit a negative event-related brain potential probably generated in the rCMA. We performed two experiments using functional magnetic resonance imaging to investigate the brain activity related to negative and positive feedback in a dynamically adaptive motion prediction task. Whereas positive feedback raised hemodynamic activity in the ventral striatum (nucleus accumbens), negative feedback activated the rCMA, the inferior anterior insula, and the epithalamus (habenular complex). These data demonstrate the role of the habenular complex in the control of the human reward system, a function previou...

Introduction: By coupling in vivo imaging with post-mortem analysis, we have previously identified an MRI correlate of dentate gyrus neurogenesis in mice. Specifically, we have relied on MRI to estimate cerebral blood volume (CBV) in the dentate gyrus and the CA1 subfields of the hippocampal formation. By adjusting dentate gyrus CBV to CA1 CBV, we were able to reliably predict the degree of cell proliferation in the dentate gyrus of mice exposed to neurogenesis manipulations. Here, we test for this MRI profile in humans with strokes, an established inducer of neurogenesis. Methods: CBV was measured with MRI in the dentate gyrus and the CA1 subfield in subjects with strokes and cognitively-matched controls. Results: Regression analysis showed that dentate gyrus CBV, adjusted for CA1 CBV, was significantly elevated in the stroke group. Secondary analysis showed that dentate gyrus CBV was significantly correlated with a functional measure of activities of daily living. Discussion: The spatial profile of CBV i...

Development of successful treatments for progressive multiple sclerosis (MS) is extremely challenging, as molecular mechanisms driving pathophysiology at this stage are poorly understood partially due to the failure of current animal models to recapitul...

Walter J. Koroshetz, MD, and Joshua Gordon, MD, PhD, are coauthors of the JNeurosci paper “The State of the NIH BRAIN Initiative,” which describes scientific advances and identifies future directions for research.

The purpose of this study was to determine which cerebral structures are activated by transcranial magnetic stimulation (TMS). To this end, we measured the effective depth (ED) of TMS, defined as the maximal distance from coil to scalp at which a motor response could be evoked. These physiological measurements were correlated with anatomical measurements obtained by magnetic resonance imaging (MRI). Motor evoked potentials (MEPs) were recorded by EMG from the first dorsal interosseus (FDI) muscle. Two intensities of stimulation (1.1 x Motor Threshold (MT) and 2 x MT) and two levels of contraction (at rest and 10% of maximal voluntary contraction, MVC) were tested with two different sized figure-of-eight coils. At rest, the ED at 1.1 x MT was 3 ± 1 mm and 6 ± 2 mm, with the small and the big coil respectively. With a stimulus of 2 x MT, the EDs increased to 12 ± 1 mm and 19 ± 3 mm. Remarkably, for all stimulus intensities the ED increased when the FDI was voluntarily activated. For example, stimulation with...

Increased adiposity can disturb glucose and lipid metabolism via disturbances in insulin sensitivity, and schizophrenia patients experience an increased prevalence of diabetes mellitus in comparison to the general population. Increased adiposity, plasma glucose and lipids are independent risk factors for cardiovascular disease, and schizophrenia patients experience increased cardiovascular (CV) mortality in comparison to the general population. Adiposity can be directly measured using whole body dual energy x-ray absorptiometry (DEXA) and abdominal magnetic resonance imaging (MRI). These adiposity measures can be analyzed in relation to whole-body glucose and lipid kinetics measured with stable isotope tracer methodology during hyperinsulinemic-euglycemic clamp conditions. Subjects included patients with schizophrenia chronically treated with antipsychotic medications, and healthy untreated controls. Patients are part of a larger study involving subsequent prospective randomized assignment to different ant...

Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large an...