The left-hand advantage seen during tactile discrimination tasks suggests hemispheric-processing asymmetry, although its neural substrates are not well known. We used functional magnetic resonance imaging to evaluate the laterality of the neural substrates involved in tactile discrimination in 19 normal volunteers. Passive tactile discrimination tasks, along with appropriate control tasks, were performed with both the right and left hands to evaluate the effects of the hand used and hemispheric effects (i.e., laterality of the activation pattern). Regardless of the hand used, the right dorsolateral prefrontal cortex, posterior parietal cortex, pre-supplementary motor area, and rostral portion of the dorsal premotor cortex (PMdr) were activated asymmetrically during tactile discrimination. This confirms the previous finding of a right-sided asymmetry for tactile shape discrimination. Hand effects were found in the left caudal portion of PMd (PMdc) adjacent to the central sulcus, which showed prominent activ...

Dopamine agonists considered selective for D3>D2 receptor subtypes induce hypolocomotion at low doses, and hyperlocomotion at higher doses, in rats. The causative mechanism is unclear[1]. We used functional magnetic resonance imaging to determine brain regions responding to doses of quinelorane known to induce either hypo- or hyperlocomotion. Male Sprague-Dawley rats (n=5) were anaesthetised with α-chloralose (60mg/kg i.v., 30mg/kg/hr) and scanned using multi-echo gradient-echo imaging (TE=5,10&15ms; TR=460ms; 120 volumes in 2 hours). Quinelorane (3 or 30µg/kg, s.c.) or saline vehicle were randomly administered 30-60 minutes after scan initiation. Mean echo images were realigned, normalised to a rat brain template and analysed using a general linear model[2]. 30µg/kg quinelorane, which induces hyperlocomotion, caused significant signal increases within the caudate-putamen, nucleus accumbens and olfactory nuclei (T>4.3, p<0.05), suggesting hyperlocomotor responses are mediated by areas rich in either D2 rec...

Estrogen has been reported to enhance cocaine sensitization in the female rat, suggesting that brain circuits mediating the rewarding and addictive properties of cocaine are affected by the gonadal steroid. The present study used functional magnetic resonance imaging (fMRI) to investigate the effect of repeated cocaine administration on blood-oxygen-level-dependent (BOLD) signal changes in fully conscious female rats without and with estrogen. Rats were ovariectomized and given subcutaneous Silastic implants without (OVX) or with estradiol benzoate (OVX+EB). Upon recovery, rats were given an i.p. cocaine injection (1 mg/kg) on 7 consecutive days. Functional MRI was performed during injections on days 1 and 7. MR Images were acquired using a 4.7T/40-cm (Oxford magnet Technology, Oxford, UK) horizontal magnet interfaced to a Paravision console (Bruker Medical Instruments, MA, USA). Anatomical data sets were acquired using a fast spin echo (RARE) sequence, (TR=2.5s; TE=56ms; field of view= 3.5x3.5cm; data mat...

Studies of patients with focal brain injury indicate that smell perception involves caudal orbitofrontal and medial temporal cortices, but a more precise functional organization has not been characterized. In addition, although it is believed that odors are potent triggers of emotion, support for an anatomical association is scant. We sought to define the neural substrates of human olfactory information processing and determine how these are modulated by affective properties of odors. We used event-related functional magnetic resonance imaging (fMRI) in an olfactory version of a classical conditioning paradigm, whereby neutral faces were paired with pleasant, neutral, or unpleasant odors, under 50% reinforcement. By comparing paired (odor/face) and unpaired (face only) conditions, odor-evoked neural activations could be isolated specifically. In primary olfactory (piriform) cortex, spatially and temporally dissociable responses were identified along a rostrocaudal axis. A nonhabituating response in posteri...

We demonstrated recently that nucleus Robustus Archistriatalis (RA) can be visualized in living canaries by Magnetic Resonance Imaging (MRI) following injection of manganese (Mn2+) in the High Vocal Center (HVc). Within a few hours Mn2+, a Ca2+ analogue, is taken up by HVc neurons. It is then transported to- and allows the visualization of RA. We investigated whether hearing conspecific songs, which affects electrical activity in HVc, can modulate the rate of RA labeling by Mn2+. Male canaries were chronically implanted with a cannula in HVc and serial MRI images were collected within the first 8 hours following Mn2+ injection on two occasions about 2-3 weeks apart in the same birds that were either exposed to conspecific songs or no songs throughout the MRI procedure. The Mn2+ uptake in RA as a function of time was fitted to a sigmoidal function providing estimates of the maximal intensity, shape of the curve and time to reach half of maximal intensity. Hearing songs induced a significant shift in the Mn2...

The blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI (fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity. We employed high-resolution mouse fMRI at 9.4 tesla to measure the BOLD response, and extracellular electrophysiological recordings to measure the effects of stimulation on single unit, multiunit, and local field potential activity. Optically driven stimulation of layer V neocortical pyramidal neurons resulted in a positive local BOLD response at the stimulated site. Consistent with a linear transform model, this locally driven BOLD response summated in response to closely spaced trains of stimulation. These properties were equivalent ...

Adjustment of response threshold for speed compared with accuracy instructions in two-choice decision-making tasks is associated with activation in the fronto-striatal network, including the pre-supplementary motor area (pre-SMA) and striatum ([Forstmann et al., 2008][1]). In contrast, increased response conservativeness is associated with activation of the subthalamic nucleus (STN) ([Frank et al., 2007][2]). We investigated the involvement of these regions in trial-by-trial adjustments of response threshold in humans, using a cued-trials task-switching paradigm. Fully and partially informative switch cues produced more conservative thresholds than repeat cues. Repeat cues were associated with higher activation in pre-SMA and striatum than switch cues. For all cue types, individual variability in response threshold was associated with activation level in pre-SMA, with higher activation linked to lower threshold setting. In the striatum, this relationship was found for repeat cues only. These findings suppo...

Present learning theories endorse the importance of synaptic plasticity; experience with a stimulus, problem, or procedure is associated with the progressive diminution in synaptic activity across most connections but increased synaptic efficiency across those that are most relevant for behavioral success. Persons with schizophrenia (SZ) may differ from normal volunteers (NV) by virtue of their inability to enhance synaptic efficiency at critical sites during learning. This visual learning study was designed to assess the ways in which SZ and NV differ in their neural response to visual recognition training. NV (n=6, mean age=29) and SZ (n=6, mean age=35) participated in two event-related functional magnetic resonance imaging studies (er_fMRI). The first was obtained prior to training and the second following completion of four training sessions. The task used a 6 second delay between the onset of the first and second stimulus (black rectangle within a frame) to assess hemodynamic response functions during...

The present study investigated the neural circuitry of affective processing in depression using event-related fMRI. Positive, negative, and neutral affective images were presented sequentially for 3 s, separated by blank screens, while BOLD signal fMRI data were acquired. Six medication-free individuals with Major Depressive Disorder or Dysthymia and six healthy controls viewed 3 runs of 63 different picture presentations. Three different time conditions provided an effective time resolution of 1s. A voxel-by-voxel 2-way (Valence x Group) ANOVA was done to examine percent signal change. Voxels exceeding the significance threshold for the interaction were further tested with planned comparison t-tests that were corrected by the Bonferroni method. Paired t-tests for the significant voxel clusters revealed differences between the negative and the neutral images for the depressed group, p's <.005. Depressed participants showed greater right prefrontal activation (tranverse frontal polar gyrus, superior frontal...

Serotonin is involved in motor control. Serotonin re-uptake inhibitors would facilitate motor recovery in post-stroke patients undergoing rehabilitation (Dam M, Stroke, 1996;27:1211-14). Fluoxetine, an inhibitor of serotonin reuptake, was shown to enhance brain motor activation in executive motor areas of healthy subjects (Loubinoux I., JCBF, 1999;19:1365-75). Effects on cerebral motor activity of a single dose (20 or 60 mg against placebo) of paroxetine (Deroxat®) were assessed in 6 healthy subjects. Either 20 mg, or 60 mg or placebo were given in 3 sessions 8 days apart, in a within subject counterbalanced, double-blinded study. 1.5T MRI scanner was used for BOLD imaging. 16 axial images, 5-mm-thick, were acquired every 3 seconds using a T2*-weighted single-shot EPI sequence. 3 runs were acquired during one session. One run consisted of eight 30-second epochs alternating between rest and activation. During activation, subjects were instructed to perform, with the right hand, the auditory 1 Hz-paced task ...