Stefan Golaszewski

Does caffeine modulate verbal working memory processes? An fMRI study.

To assess the effect of caffeine on the functional MRI signal during a 2-back verbal working memory task, we examined blood oxygenation level-dependent regional brain activity in 15 healthy right-handed males. The subjects, all moderate caffeine consumers, underwent two scanning sessions on a 1.5-T MR-Scanner separated by a 24- to 48-h interval. Each participant received either placebo or 100 mg caffeine 20 min prior to the performance of the working memory task in blinded crossover fashion. The study was implemented as a blocked-design. Analysis was performed using SPM2. In both conditions, the characteristic working memory network of frontoparietal cortical activation including the precuneus and the anterior cingulate could be shown. In comparison to placebo, caffeine caused an increased response in the bilateral medial frontopolar cortex (BA 10), extending to the right anterior cingulate cortex (BA 32). These results suggest that caffeine modulates neuronal activity as evidenced by fMRI signal changes in a network of brain areas associated with executive and attentional functions during working memory processes.

Functional brain reorganization after spinal cord injury: Systematic review of animal and human studies

Plastic changes of neural circuits occur after spinal cord injury (SCI) at various level of the central nervous system. In this review we will focus on delineating the pathophysiological mechanisms of the brain plasticity changes following SCI, based on the existing neuroimaging and neurophysiological evidence in experimental models and humans. In animal experiments, reorganization of the sensory topography as well as of the topographical map of primary motor and premotor cortices have been reported in several studies. Brain imaging revealed that cortical representation in response to spared forelimb stimulation early enlarges and invades adjacent sensory-deprived hind limb territory. Electrophysiological studies demonstrated that the deafferentation due to SCI can immediately change the state of large cortical networks within 1h, and that these changes play a critical role in the functional reorganization after SCI. In humans neuroimaging also showed shifts of functional motor and sensory cortical representations that relate to the severity of SCI. In patients with cervical SCI, cortical forearm motor representations, as assessed by means of transcranial magnetic stimulation, may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm. Excessive or aberrant reorganisation of cerebral cortex may also have pathological consequences, such as phantom sensations or neuropathic pain. Integrated neuroimaging and neurophysiological approaches may also lead to the development of new therapeutic strategies, which have the potential of enhancing sensorimotor recovery in patients with SCI.

Functional magnetic resonance imaging of the human sensorimotor cortex using a novel vibrotactile stimulator.

The purpose of this study was to investigate the fMRI response of the sensorimotor cortex to a vibration paradigm produced by a novel vibrotactile stimulator. Fifteen contiguous slices covering the sensorimotor cortex parallel to the anterior (AC) and posterior commissure (PC) line were obtained with echoplanar magnetic resonance imaging at 1.5T. Cortical activity in ten healthy subjects (20-45 years) was investigated during vibration (50 Hz) of the palm of the right hand and compared to a finger-to-thumb tapping paradigm. For the vibration paradigm a mechanically driven vibration head was mounted on the palm of the right hand. The new vibration device produces vibration frequencies (1-130 Hz) and displacement amplitudes (0.5-4 mm) suitable to elicit the tonic vibratory reflex. The fMRI measurement during vibratory stimulation revealed activation in the pre- and postcentral gyrus in all subjects. These activations were comparable to the finger-to-thumb tapping paradigm. The advantages of the new MR compatible vibration device include effective transmission of the stimulus and controlled vibration frequencies and intensities. These preliminary fMRI results indicate that vibration can be an alternative paradigm for the evaluation of sensory and motor functions in patients unable to perform active motor paradigms.

Modulatory effects on human sensorimotor cortex by whole-hand afferent electrical stimulation

Objective: To investigate the effect of electrical stimulation of the nerve afferents of the hand on cortical activity elicited by whole-hand subthreshold stimulation for sensation in healthy human subjects. Methods: Ten healthy volunteers were studied using BOLD-fMRI with 1) a test motor-task with finger-to-thumb tapping of the left hand, 2) a whole-hand afferent electrical stimulation of the left hand below the sensory level for sensation for 30 minutes, 3) a second fMRI run with the same paradigm as in the test motor-task immediately after electrical stimulation, and 4) a final identical fMRI run 2 hours post-stimulation to test the cortical changes induced by electrical stimulation. Experiments were carried out on a 1.5 T MR scanner and for fMRI echoplanar sequences were used. Data analysis was performed with SPM99. Results: An increase of movement-related responses was seen within the primary motor and primary somatosensory areas of both hemispheres when comparing the test motor-task with the motor-task after electrical stimulation relative to the baseline or sham stimulation. Two hours post-stimulation the modulatory effects of mesh-glove stimulation diminished to baseline level except within the contralateral primary motor region. Conclusions: The increased BOLD response spatially localized within the sensorimotor cortex reflects an increase in neuronal activity that may provide augmented neuronal excitability.

Deactivation of the Default Mode Network as a Marker of Impaired Consciousness: An fMRI Study

Diagnosis of patients with a disorder of consciousness is very challenging. Previous studies investigating resting state networks demonstrate that 2 main features of the so-called default mode network (DMN), metabolism and functional connectivity, are impaired in patients with a disorder of consciousness. However, task-induced deactivation – a third main feature of the DMN – has not been explored in a group of patients. Deactivation of the DMN is supposed to reflect interruptions of introspective processes. Seventeen patients with unresponsive wakefulness syndrome (UWS, former vegetative state), 8 patients in minimally conscious state (MCS), and 25 healthy controls were investigated with functional magnetic resonance imaging during a passive sentence listening task. Results show that deactivation in medial regions is reduced in MCS and absent in UWS patients compared to healthy controls. Moreover, behavioral scores assessing the level of consciousness correlate with deactivation in patients. On single-subject level, all control subjects but only 2 patients in MCS and 6 with UWS exposed deactivation. Interestingly, all patients who deactivated during speech processing (except for one) showed activation in left frontal regions which are associated with conscious processing. Our results indicate that deactivation of the DMN can be associated with the level of consciousness by selecting those who are able to interrupt ongoing introspective processes. In consequence, deactivation of the DMN may function as a marker of consciousness.

Laser acupuncture induced specific cerebral cortical and subcortical activations in humans

As recent studies demonstrated, acupuncture can elicit activity in specific brain areas. This study aims to explore further the central effect using laser acupuncture. We investigated the cerebral effects of laser acupuncture at both acupoints GB43 with functional magnetic resonance imaging (fMRI). As a control condition the laser was mounted at the same acupoints but without application of laser stimulation. The group results showed significant brain activations within the thalamus, nucleus subthalamicus, nucleus ruber, the brainstem, and the Brodmann areas 40 and 22 for the acupuncture condition. No significant brain activations were observed within the placebo condition. The activations we observed were laser acupuncture-specific and predominantly ipsilateral. This supports the assumption that acupuncture is mediated by meridians, since meridians do not cross to the other side. Furthermore, we could show that laser acupuncture allows one to design a pure placebo condition.

Effect of Transcranial Brain Stimulation for the Treatment of Alzheimer Disease: A Review

Available pharmacological treatments for Alzheimer disease (AD) have limited effectiveness, are expensive, and sometimes induce side effects. Therefore, alternative or complementary adjuvant therapeutic strategies have gained increasing attention. The development of novel noninvasive methods of brain stimulation has increased the interest in neuromodulatory techniques as potential therapeutic tool for cognitive rehabilitation in AD. In particular, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive approaches that induce prolonged functional changes in the cerebral cortex. Several studies have begun to therapeutically use rTMS or tDCS to improve cognitive performances in patients with AD. However, most of them induced short-duration beneficial effects and were not adequately powered to establish evidence for therapeutic efficacy. Therefore, TMS and tDCS approaches, seeking to enhance cognitive function, have to be considered still very preliminary. In future studies, multiple rTMS or tDCS sessions might also interact, and metaplasticity effects could affect the outcome.

Abnormal short latency afferent inhibition in early Alzheimer’s disease: a transcranial magnetic demonstration

The pathogenesis of Alzheimer’s disease (AD) appears to involve several different mechanisms, the most consistent of which is an impairment of cholinergic neurotransmission; however, there is controversy about its relevance at the early stage of disease. A transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI) may give direct information about the function of some cholinergic pathways in the human motor cortex. We evaluated SAI in a group of patients with early diagnosis of AD and compared the data with that from a control group. The amount of SAI was significantly smaller in early AD patients than in controls. This study first provides physiological evidence that a central cholinergic dysfunction occurs in the earlier stages of AD. Identification of SAI abnormalities that occur early in the course of AD will allow earlier diagnosis and treatment with cholinergic drugs.

A new pneumatic vibrator for functional magnetic resonance imaging of the human sensorimotor cortex.

The aim of the study was to implement a vibrotactile stimulator using functional magnetic resonance imaging (fMRI). A fMRI compatible vibration device consisting of a pneumatically driven dual membrane pump was developed. Brain activation during 50 Hz vibrotactile stimulation of the right hand-palm were compared to a right 2 Hz finger-to-thumb-tapping in ten healthy, right-handed male volunteers. The vibration paradigm showed a comparable activation pattern with respect to finger-to-thumb-tapping in the contralateral perirolandic region. The advantage of the new vibration device is the possibility to elicit the vibratory-tonic-reflex due to the higher amplitude in context with the high frequency than established devices. This reflex is considered to be responsible for the activation in the primary motor cortex and the current paradigm might prove useful in future neurosurgical planning in patients with perirolandic lesions.

Short latency afferent inhibition differs among the subtypes of mild cognitive impairment

Mild cognitive impairment (MCI) is considered a transitional stage between normal aging and a diagnosis of clinically probable Alzheimer disease (AD). The role of the cholinergic system in MCI is not clearly defined and needs to be further investigated. A transcranial magnetic stimulation (TMS) protocol, the short latency afferent inhibition (SAI), may give direct information about the function of some cholinergic pathways in the human motor cortex. We aimed to evaluate in the present study the relationship of SAI to the specific clinical subtypes of MCI. SAI was examined in 20 patients with amnestic MCI (10 SD, 10 MD), twenty patients with nonamnestic MCI (10 SD, 10 MD) and ten control subjects. Motor threshold, central motor conduction time, intracortical inhibition and facilitation to paired-TMS were also evaluated. Mean SAI was significantly reduced in amnestic MCI-MD patients when compared with the controls, while it was not significantly different in amnestic MCI-SD patients and in nonamnestic patients. SAI was increased after administration of a single dose of donepezil in a subgroup of four amnestic MCI-MD patients. The other TMS parameters did not differ significantly between the four MCI groups and the control group. We demonstrated that this putative marker of central cholinergic activity differs among MCI subtypes. The amnestic-MD type of MCI might be a phenotype of incipient AD. However, this hypothesis would be better addressed in a longitudinal study of individual patients. TMS studies may be useful in identifying MCI individuals in whom cholinergic degeneration is occurred and therefore at increased risk of conversion to AD.