Arne May

Neuroplasticity: Changes in grey matter induced by training

Does the structure of an adult human brain alter in response to environmental demands? Here we use whole-brain magnetic-resonance imaging to visualize learning-induced plasticity in the brains of volunteers who have learned to juggle. We find that these individuals show a transient and selective structural change in brain areas that are associated with the processing and storage of complex visual motion. This discovery of a stimulus-dependent alteration in the brains macroscopic structure contradicts the traditionally held view that cortical plasticity is associated with functional rather than anatomical changes.

Hypothalamic activation in cluster headache attacks

BACKGROUND Cluster headache, one of the most severe pain syndromes in human beings, is usually described as a vascular headache. However, the striking circadian rhythmicity of this strictly half-sided pain syndrome cannot be readily explained by the vascular hypothesis. We aimed to assess changes in regional cerebral blood flow (rCBF) in patients with cluster headache. METHODS We used positron emission tomography (PET) to assess the changes in rCBF, as an index of synaptic activity, during nitroglycerin-induced cluster headache attacks in nine patients who had chronic cluster headache. Eight patients who had cluster headache but were not in the bout acted as a control group. FINDINGS In the acute pain state, activation was seen in the ipsilateral inferior hypothalamic grey matter, the contralateral ventroposterior thalamus, the anterior cingulate cortex, and bilaterally in the insulae. Activation in the hypothalamus was seen solely in the pain state and was not seen in patients who have cluster headache but were out of the bout. INTERPRETATION Our findings establish central nervous system dysfunction in the region of the hypothalamus as the primum movens in the pathophysiology of cluster headache. We suggest that a radical reappraisal of this type of headache is needed and that it should in general terms, be regarded as a neurovascular headache, to give equal weight to the pathological and physiological mechanisms that are at work.

Temporal and Spatial Dynamics of Brain Structure Changes during Extensive Learning

The current view regarding human long-term memory as an active process of encoding and retrieval includes a highly specific learning-induced functional plasticity in a network of multiple memory systems. Voxel-based morphometry was used to detect possible structural brain changes associated with learning. Magnetic resonance images were obtained at three different time points while medical students learned for their medical examination. During the learning period, the gray matter increased significantly in the posterior and lateral parietal cortex bilaterally. These structural changes did not change significantly toward the third scan during the semester break 3 months after the exam. The posterior hippocampus showed a different pattern over time: the initial increase in gray matter during the learning period was even more pronounced toward the third time point. These results indicate that the acquisition of a great amount of highly abstract information may be related to a particular pattern of structural gray matter changes in particular brain areas.

Training-Induced Brain Structure Changes in the Elderly

It has been suggested that learning is associated with a transient and highly selective increase in brain gray matter in healthy young volunteers. It is not clear whether and to what extent the aging brain is still able to exhibit such structural plasticity. We built on our original study, now focusing on healthy senior citizens. We observed that elderly persons were able to learn three-ball cascade juggling, but with less proficiency compared with 20-year-old adolescents. Similar to the young group, gray-matter changes in the older brain related to skill acquisition were observed in area hMT/V5 (middle temporal area of the visual cortex). In addition, elderly volunteers who learned to juggle showed transient increases in gray matter in the hippocampus on the left side and in the nucleus accumbens bilaterally.

EFNS guideline on the drug treatment of migraine – revised report of an EFNS task force

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients’ quality of life. To give evidence‐based or expert recommendations for the different drug treatment procedures of the different migraine syndromes based on a literature search and an consensus in an expert panel. All available medical reference systems were screened for all kinds of clinical studies on migraine with and without aura and on migraine‐like syndromes. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A,B, or C recommendations and good practice points. For the acute treatment of migraine attacks, oral non‐steroidal anti‐inflammatory drugs (NSAIDs) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAIDs and triptans, oral metoclopramide or domperidon is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. A status migrainosus can probably be treated by steroids. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis are amitriptyline, naproxen, petasites, and bisoprolol.

The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation.

Primary headache syndromes, such as cluster headache and migraine, are widely described as vascular headaches, although considerable clinical evidence suggests that both are primarily driven from the brain. The shared anatomical and physiologic substrate for both of these clinical problems is the neural innervation of the cranial circulation. Functional imaging with positron emission tomography has shed light on the genesis of both syndromes, documenting activation in the midbrain and pons in migraine and in the hypothalamic gray in cluster headache. These areas are involved in the pain process in a permissive or triggering manner rather than as a response to first-division nociceptive pain impulses. In a positron emission tomography study in cluster headache, however, activation in the region of the major basal arteries was observed. This is likely to result from vasodilation of these vessels during the acute pain attack as opposed to the rest state in cluster headache, and represents the first convincing activation of neural vasodilator mechanisms in humans. The observation of vasodilation was also made in an experimental trigeminal pain study, which concluded that the observed dilation of these vessels in trigeminal pain is not inherent to a specific headache syndrome, but rather is a feature of the trigeminal neural innervation of the cranial circulation. Clinical and animal data suggest that the observed vasodilation is, in part, an effect of a trigeminoparasympathetic reflex. The data presented here review these developments in the physiology of the trigeminovascular system, which demand renewed consideration of the neural influences at work in many primary headaches and, thus, further consideration of the physiology of the neural innervation of the cranial circulation. We take the view that the known physiologic and pathophysiologic mechanisms of the systems involved dictate that these disorders should be collectively regarded as neurovascular headaches to emphasize the interaction between nerves and vessels, which is the underlying characteristic of these syndromes. Moreover, the syndromes can be understood only by a detailed study of the cerebrovascular physiologic mechanisms that underpin their expression.

Cluster headache A prospective clinical study with diagnostic implications

BackgroundCluster headache, when compared with migraine or tension-type headache, is an uncommon form of primary neurovascular headache. However, with a prevalence of approximately 0.1% and a lengthy history of disabling and distressing episodic pain, cluster headache is an important neurologic problem. MethodsPatients (n = 230) were recruited from our specialist clinic (24%) or from support groups (76%). All patients had a detailed history taken by at least two physicians and were assigned diagnoses according to the International Headache Society Diagnostic Guidelines. ResultsThe pain characteristics were of a strictly unilateral, predominantly retro-orbital (92%) and temporal pain (70%). Of the cranial autonomic features, lacrimation (91%) was the most common. Nausea (50%), photophobia (56%), and phonophobia (43%) often were noted, as was a sense of agitation or restlessness in 93% of patients. Typical migrainous aura was noted in 14% of this cohort. Most patients (79%) had episodic cluster headache, which was largely the same clinically as chronic cluster headache except for the persistence of attacks over time. The overall male-to-female ratio in this sample was 2.5:1, and this has decreased with time. Neither oral contraceptive use, menses, menopause, nor hormone replacement therapy had any consistent effect on cluster headache in women. Less than half of the patients had tried injectable sumatriptan, and many had not tried high-flow oxygen. Several unproven preventative agents that usually are used in migraine and an array of alternative therapies had been used; none of the latter was consistently effective. ConclusionPatients with cluster headache offer a population of primary headache patients with devastating acute attacks of pain. The syndrome is stereotyped with effective evidence-based treatments that are prescribed in only half of patients having cluster headache.

Changes in Gray Matter Induced by Learning—Revisited

Background Recently, activation-dependant structural brain plasticity in humans has been demonstrated in adults after three months of training a visio-motor skill. Learning three-ball cascade juggling was associated with a transient and highly selective increase in brain gray matter in the occipito-temporal cortex comprising the motion sensitive area hMT/V5 bilaterally. However, the exact time-scale of usage-dependant structural changes occur is still unknown. A better understanding of the temporal parameters may help to elucidate to what extent this type of cortical plasticity contributes to fast adapting cortical processes that may be relevant to learning. Principal Findings Using a 3 Tesla scanner and monitoring whole brain structure we repeated and extended our original study in 20 healthy adult volunteers, focussing on the temporal aspects of the structural changes and investigated whether these changes are performance or exercise dependant. The data confirmed our earlier observation using a mean effects analysis and in addition showed that learning to juggle can alter gray matter in the occipito-temporal cortex as early as after 7 days of training. Neither performance nor exercise alone could explain these changes. Conclusion We suggest that the qualitative change (i.e. learning of a new task) is more critical for the brain to change its structure than continued training of an already-learned task.

Training-induced structural changes in the adult human brain

Structural and functional brain reorganisation can occur beyond the developmental maturation period and this was recently recognised as an intrinsic property of the human central nervous system. Brain injury or altered afferent input due to environmental changes, novel experience and learning new skills are known as modulators of brain function and underlying neuroanatomic circuitry. During the past decade invasive animal studies and in vivo imaging techniques have delineated the correlates of experience dependent reorganisation. The major future challenge is to understand the behavioural consequences and cellular mechanisms underlying training-induced neuroanatomic plasticity in order to adapt treatment strategies for patients with brain injury or neurodegenerative disorders.

Gray matter decrease in patients with chronic tension type headache

Using MRI and voxel-based morphometry, the authors investigated 20 patients with chronic tension type headache (CTTH) and 20 patients with medication-overuse headache and compared them to 40 controls with no headache history. Only patients with CTTH demonstrated a significant gray matter decrease in regions known to be involved in pain processing. The finding implies that the alterations are specific to CTTH rather than a response to chronic head pain or chronification per se.